Nucleic Acids Biochemistry

  1. Nucleic Acid Metabolism: Biosynthesis
    1. Biosynthesis of Nucleotides
      1. De Novo Pathways
        1. Purine Synthesis Pathway
          1. Key Intermediates
            1. 5-Phosphoribosyl-1-pyrophosphate
              1. Inosine Monophosphate
                1. Adenosine Monophosphate
                  1. Guanosine Monophosphate
                  2. Enzymatic Steps
                    1. PRPP Synthetase
                      1. Amidophosphoribosyltransferase
                        1. IMP Dehydrogenase
                          1. Adenylosuccinate Synthetase
                          2. Regulation Mechanisms
                            1. Feedback Inhibition
                              1. Allosteric Control
                                1. Compartmentalization
                              2. Pyrimidine Synthesis Pathway
                                1. Key Intermediates
                                  1. Carbamoyl Phosphate
                                    1. Orotic Acid
                                      1. Uridine Monophosphate
                                        1. Cytidine Triphosphate
                                        2. Enzymatic Steps
                                          1. Carbamoyl Phosphate Synthetase II
                                            1. Aspartate Transcarbamoylase
                                              1. Orotate Phosphoribosyltransferase
                                                1. CTP Synthetase
                                                2. Regulation Mechanisms
                                                  1. Feedback Inhibition
                                                    1. Allosteric Control
                                                      1. Transcriptional Control
                                                  2. Salvage Pathways
                                                    1. Purine Salvage
                                                      1. Hypoxanthine-Guanine Phosphoribosyltransferase
                                                        1. Adenine Phosphoribosyltransferase
                                                          1. Clinical Significance
                                                          2. Pyrimidine Salvage
                                                            1. Uracil Phosphoribosyltransferase
                                                              1. Thymidine Kinase
                                                                1. Cytidine Deaminase
                                                              2. Regulation of Nucleotide Synthesis
                                                                1. Feedback Inhibition Mechanisms
                                                                  1. End Product Inhibition
                                                                    1. Competitive Inhibition
                                                                      1. Non-Competitive Inhibition
                                                                      2. Allosteric Regulation
                                                                        1. Positive Effectors
                                                                          1. Negative Effectors
                                                                            1. Cooperative Binding
                                                                            2. Transcriptional Control
                                                                              1. Gene Expression Regulation
                                                                                1. Cell Cycle Dependence
                                                                              2. Formation of Deoxyribonucleotides
                                                                                1. Ribonucleotide Reductase Mechanism
                                                                                  1. Enzyme Structure
                                                                                    1. Radical Chemistry
                                                                                      1. Substrate Specificity
                                                                                        1. Allosteric Regulation
                                                                                        2. Regulation of Deoxyribonucleotide Pools
                                                                                          1. Cell Cycle Control
                                                                                            1. Balanced Pool Maintenance
                                                                                              1. Inhibitor Mechanisms
                                                                                          2. DNA Replication
                                                                                            1. Semiconservative Mechanism
                                                                                              1. Meselson-Stahl Experiment
                                                                                                1. Conservative vs Dispersive Models
                                                                                                  1. Experimental Evidence
                                                                                                  2. Origin of Replication
                                                                                                    1. Prokaryotic Origins
                                                                                                      1. oriC Structure
                                                                                                        1. DnaA Binding Sites
                                                                                                          1. AT-Rich Regions
                                                                                                          2. Eukaryotic Origins
                                                                                                            1. Origin Recognition Complex
                                                                                                              1. Multiple Origins
                                                                                                                1. Timing Control
                                                                                                              2. The Replication Fork
                                                                                                                1. Fork Structure
                                                                                                                  1. Leading Strand Template
                                                                                                                    1. Lagging Strand Template
                                                                                                                      1. Replication Machinery
                                                                                                                      2. Fork Movement
                                                                                                                        1. Helicase Activity
                                                                                                                          1. Topological Problems
                                                                                                                            1. Coordination Mechanisms
                                                                                                                          2. Key Enzymes and Proteins
                                                                                                                            1. DNA Polymerases
                                                                                                                              1. Prokaryotic DNA Polymerases
                                                                                                                                1. DNA Polymerase I
                                                                                                                                  1. DNA Polymerase II
                                                                                                                                    1. DNA Polymerase III
                                                                                                                                    2. Eukaryotic DNA Polymerases
                                                                                                                                      1. DNA Polymerase α
                                                                                                                                        1. DNA Polymerase δ
                                                                                                                                          1. DNA Polymerase ε
                                                                                                                                          2. Polymerase Properties
                                                                                                                                            1. 3' to 5' Exonuclease Activity
                                                                                                                                              1. Processivity
                                                                                                                                                1. Fidelity
                                                                                                                                              2. Helicase Enzymes
                                                                                                                                                1. DnaB Helicase
                                                                                                                                                  1. MCM Complex
                                                                                                                                                    1. Unwinding Mechanism
                                                                                                                                                    2. Primase Function
                                                                                                                                                      1. RNA Primer Synthesis
                                                                                                                                                        1. Primer Length
                                                                                                                                                          1. Primer Removal
                                                                                                                                                          2. Single-Strand Binding Proteins
                                                                                                                                                            1. SSB Protein Function
                                                                                                                                                              1. RPA Complex
                                                                                                                                                                1. Cooperative Binding
                                                                                                                                                                2. DNA Ligase
                                                                                                                                                                  1. Nick Sealing
                                                                                                                                                                    1. ATP vs NAD+ Dependence
                                                                                                                                                                      1. Substrate Specificity
                                                                                                                                                                      2. Sliding Clamp and Clamp Loader
                                                                                                                                                                        1. PCNA Structure
                                                                                                                                                                          1. β-Clamp Function
                                                                                                                                                                            1. RFC Complex
                                                                                                                                                                          2. Mechanism of Replication
                                                                                                                                                                            1. Initiation Process
                                                                                                                                                                              1. Recognition of Origin
                                                                                                                                                                                1. Origin Binding Proteins
                                                                                                                                                                                  1. Chromatin Remodeling
                                                                                                                                                                                    1. Licensing Control
                                                                                                                                                                                    2. Assembly of Initiation Complex
                                                                                                                                                                                      1. Pre-Replication Complex
                                                                                                                                                                                        1. Helicase Loading
                                                                                                                                                                                          1. Primer Synthesis
                                                                                                                                                                                        2. Elongation Process
                                                                                                                                                                                          1. Leading Strand Synthesis
                                                                                                                                                                                            1. Continuous Synthesis
                                                                                                                                                                                              1. Polymerase Coupling
                                                                                                                                                                                                1. Proofreading Activity
                                                                                                                                                                                                2. Lagging Strand Synthesis
                                                                                                                                                                                                  1. Discontinuous Synthesis
                                                                                                                                                                                                    1. Okazaki Fragment Formation
                                                                                                                                                                                                      1. Primer Processing
                                                                                                                                                                                                      2. Coordination Mechanisms
                                                                                                                                                                                                        1. Replisome Organization
                                                                                                                                                                                                          1. Trombone Model
                                                                                                                                                                                                            1. Quality Control
                                                                                                                                                                                                          2. Termination Process
                                                                                                                                                                                                            1. Termination Sequences
                                                                                                                                                                                                              1. Ter Sites
                                                                                                                                                                                                                1. Tus Protein Binding
                                                                                                                                                                                                                2. Fork Collision
                                                                                                                                                                                                                  1. Replication Fork Meeting
                                                                                                                                                                                                                    1. Topological Resolution
                                                                                                                                                                                                                    2. Disassembly of Replication Machinery
                                                                                                                                                                                                                      1. Polymerase Dissociation
                                                                                                                                                                                                                        1. Chromatin Restoration
                                                                                                                                                                                                                    3. Replication in Prokaryotes vs Eukaryotes
                                                                                                                                                                                                                      1. Number of Origins
                                                                                                                                                                                                                        1. Single Origin in Prokaryotes
                                                                                                                                                                                                                          1. Multiple Origins in Eukaryotes
                                                                                                                                                                                                                            1. Origin Spacing
                                                                                                                                                                                                                            2. Replication Timing
                                                                                                                                                                                                                              1. S Phase Control
                                                                                                                                                                                                                                1. Origin Firing
                                                                                                                                                                                                                                  1. Checkpoint Control
                                                                                                                                                                                                                                  2. Replication Complexes
                                                                                                                                                                                                                                    1. Replisome Differences
                                                                                                                                                                                                                                      1. Accessory Factors
                                                                                                                                                                                                                                        1. Chromatin Context
                                                                                                                                                                                                                                      2. Telomeres and Telomerase
                                                                                                                                                                                                                                        1. Structure of Telomeres
                                                                                                                                                                                                                                          1. Telomeric DNA Sequences
                                                                                                                                                                                                                                            1. T-Loop Formation
                                                                                                                                                                                                                                              1. Shelterin Complex
                                                                                                                                                                                                                                              2. End-Replication Problem
                                                                                                                                                                                                                                                1. 5' End Synthesis Issue
                                                                                                                                                                                                                                                  1. Progressive Shortening
                                                                                                                                                                                                                                                    1. Cellular Senescence
                                                                                                                                                                                                                                                    2. Telomerase Mechanism
                                                                                                                                                                                                                                                      1. Reverse Transcriptase Activity
                                                                                                                                                                                                                                                        1. RNA Template Component
                                                                                                                                                                                                                                                          1. Processivity Control
                                                                                                                                                                                                                                                          2. Telomere Maintenance
                                                                                                                                                                                                                                                            1. Stem Cell Telomerase
                                                                                                                                                                                                                                                              1. Cancer Cell Activation
                                                                                                                                                                                                                                                                1. Alternative Lengthening
                                                                                                                                                                                                                                                            2. Transcription: DNA-Directed RNA Synthesis
                                                                                                                                                                                                                                                              1. The Transcription Unit
                                                                                                                                                                                                                                                                1. Promoters
                                                                                                                                                                                                                                                                  1. Core Promoter Elements
                                                                                                                                                                                                                                                                    1. TATA Box
                                                                                                                                                                                                                                                                      1. Initiator Elements
                                                                                                                                                                                                                                                                        1. CAAT Box
                                                                                                                                                                                                                                                                          1. GC Box
                                                                                                                                                                                                                                                                          2. Regulatory Elements
                                                                                                                                                                                                                                                                            1. Enhancers
                                                                                                                                                                                                                                                                              1. Silencers
                                                                                                                                                                                                                                                                                1. Response Elements
                                                                                                                                                                                                                                                                              2. Coding Region
                                                                                                                                                                                                                                                                                1. Transcribed Sequences
                                                                                                                                                                                                                                                                                  1. Intron-Exon Structure
                                                                                                                                                                                                                                                                                    1. Regulatory Sequences
                                                                                                                                                                                                                                                                                    2. Terminator Sequences
                                                                                                                                                                                                                                                                                      1. Intrinsic Terminators
                                                                                                                                                                                                                                                                                        1. Extrinsic Terminators
                                                                                                                                                                                                                                                                                          1. Polyadenylation Signals
                                                                                                                                                                                                                                                                                        2. RNA Polymerases
                                                                                                                                                                                                                                                                                          1. Prokaryotic RNA Polymerase
                                                                                                                                                                                                                                                                                            1. Core Enzyme Structure
                                                                                                                                                                                                                                                                                              1. Sigma Factor Function
                                                                                                                                                                                                                                                                                                1. Holoenzyme Assembly
                                                                                                                                                                                                                                                                                                2. Eukaryotic RNA Polymerases
                                                                                                                                                                                                                                                                                                  1. RNA Polymerase I
                                                                                                                                                                                                                                                                                                    1. rRNA Gene Transcription
                                                                                                                                                                                                                                                                                                      1. Promoter Recognition
                                                                                                                                                                                                                                                                                                        1. Transcription Factors
                                                                                                                                                                                                                                                                                                        2. RNA Polymerase II
                                                                                                                                                                                                                                                                                                          1. mRNA Gene Transcription
                                                                                                                                                                                                                                                                                                            1. CTD Phosphorylation
                                                                                                                                                                                                                                                                                                              1. Mediator Complex
                                                                                                                                                                                                                                                                                                              2. RNA Polymerase III
                                                                                                                                                                                                                                                                                                                1. tRNA Gene Transcription
                                                                                                                                                                                                                                                                                                                  1. Internal Promoters
                                                                                                                                                                                                                                                                                                                    1. TFIIIB Complex
                                                                                                                                                                                                                                                                                                                2. The Process of Transcription
                                                                                                                                                                                                                                                                                                                  1. Initiation Process
                                                                                                                                                                                                                                                                                                                    1. Promoter Recognition
                                                                                                                                                                                                                                                                                                                      1. Transcription Factor Binding
                                                                                                                                                                                                                                                                                                                        1. DNA Melting
                                                                                                                                                                                                                                                                                                                          1. Open Complex Formation
                                                                                                                                                                                                                                                                                                                          2. Assembly of Pre-Initiation Complex
                                                                                                                                                                                                                                                                                                                            1. General Transcription Factors
                                                                                                                                                                                                                                                                                                                              1. Mediator Recruitment
                                                                                                                                                                                                                                                                                                                                1. Chromatin Remodeling
                                                                                                                                                                                                                                                                                                                                2. Promoter Clearance
                                                                                                                                                                                                                                                                                                                                  1. Abortive Initiation
                                                                                                                                                                                                                                                                                                                                    1. Productive Elongation
                                                                                                                                                                                                                                                                                                                                      1. Factor Release
                                                                                                                                                                                                                                                                                                                                    2. Elongation Process
                                                                                                                                                                                                                                                                                                                                      1. RNA Chain Growth
                                                                                                                                                                                                                                                                                                                                        1. Nucleotide Addition
                                                                                                                                                                                                                                                                                                                                          1. Translocation
                                                                                                                                                                                                                                                                                                                                            1. Processivity
                                                                                                                                                                                                                                                                                                                                            2. Transcriptional Pausing
                                                                                                                                                                                                                                                                                                                                              1. Pause Sites
                                                                                                                                                                                                                                                                                                                                                1. Elongation Factors
                                                                                                                                                                                                                                                                                                                                                  1. Anti-Termination
                                                                                                                                                                                                                                                                                                                                                  2. Proofreading Mechanisms
                                                                                                                                                                                                                                                                                                                                                    1. 3' to 5' Exonuclease Activity
                                                                                                                                                                                                                                                                                                                                                      1. Transcript Cleavage
                                                                                                                                                                                                                                                                                                                                                        1. Error Correction
                                                                                                                                                                                                                                                                                                                                                      2. Termination Process
                                                                                                                                                                                                                                                                                                                                                        1. Rho-Dependent Termination
                                                                                                                                                                                                                                                                                                                                                          1. Rho Protein Function
                                                                                                                                                                                                                                                                                                                                                            1. ATP-Dependent Mechanism
                                                                                                                                                                                                                                                                                                                                                              1. Rut Sites
                                                                                                                                                                                                                                                                                                                                                              2. Rho-Independent Termination
                                                                                                                                                                                                                                                                                                                                                                1. Hairpin Formation
                                                                                                                                                                                                                                                                                                                                                                  1. Poly-U Tract
                                                                                                                                                                                                                                                                                                                                                                    1. Intrinsic Termination
                                                                                                                                                                                                                                                                                                                                                                    2. Polyadenylation-Coupled Termination
                                                                                                                                                                                                                                                                                                                                                                      1. Cleavage and Polyadenylation
                                                                                                                                                                                                                                                                                                                                                                        1. Torpedo Model
                                                                                                                                                                                                                                                                                                                                                                          1. Allosteric Model
                                                                                                                                                                                                                                                                                                                                                                      2. Post-Transcriptional Processing in Eukaryotes
                                                                                                                                                                                                                                                                                                                                                                        1. 5' Capping
                                                                                                                                                                                                                                                                                                                                                                          1. Enzymatic Steps
                                                                                                                                                                                                                                                                                                                                                                            1. Phosphatase Activity
                                                                                                                                                                                                                                                                                                                                                                              1. Guanylyltransferase Activity
                                                                                                                                                                                                                                                                                                                                                                                1. Methyltransferase Activity
                                                                                                                                                                                                                                                                                                                                                                                2. Cap Structure
                                                                                                                                                                                                                                                                                                                                                                                  1. 7-Methylguanosine Cap
                                                                                                                                                                                                                                                                                                                                                                                    1. 5'-5' Triphosphate Linkage
                                                                                                                                                                                                                                                                                                                                                                                      1. Additional Methylations
                                                                                                                                                                                                                                                                                                                                                                                      2. Functions of the Cap
                                                                                                                                                                                                                                                                                                                                                                                        1. Translation Initiation
                                                                                                                                                                                                                                                                                                                                                                                          1. mRNA Stability
                                                                                                                                                                                                                                                                                                                                                                                            1. Nuclear Export
                                                                                                                                                                                                                                                                                                                                                                                          2. 3' Polyadenylation
                                                                                                                                                                                                                                                                                                                                                                                            1. Polyadenylation Signal
                                                                                                                                                                                                                                                                                                                                                                                              1. AAUAAA Sequence
                                                                                                                                                                                                                                                                                                                                                                                                1. GU-Rich Element
                                                                                                                                                                                                                                                                                                                                                                                                  1. Cleavage Site
                                                                                                                                                                                                                                                                                                                                                                                                  2. Cleavage and Polyadenylation Specificity Factor
                                                                                                                                                                                                                                                                                                                                                                                                    1. CPSF Complex
                                                                                                                                                                                                                                                                                                                                                                                                      1. CstF Complex
                                                                                                                                                                                                                                                                                                                                                                                                        1. CFI and CFII
                                                                                                                                                                                                                                                                                                                                                                                                        2. Poly(A) Polymerase
                                                                                                                                                                                                                                                                                                                                                                                                          1. PAP Activity
                                                                                                                                                                                                                                                                                                                                                                                                            1. Poly(A) Binding Protein
                                                                                                                                                                                                                                                                                                                                                                                                              1. Length Control
                                                                                                                                                                                                                                                                                                                                                                                                              2. Functions of the Poly(A) Tail
                                                                                                                                                                                                                                                                                                                                                                                                                1. Translation Enhancement
                                                                                                                                                                                                                                                                                                                                                                                                                  1. mRNA Stability
                                                                                                                                                                                                                                                                                                                                                                                                                    1. Cytoplasmic Localization
                                                                                                                                                                                                                                                                                                                                                                                                                  2. RNA Splicing
                                                                                                                                                                                                                                                                                                                                                                                                                    1. Introns and Exons
                                                                                                                                                                                                                                                                                                                                                                                                                      1. Splice Site Sequences
                                                                                                                                                                                                                                                                                                                                                                                                                        1. Branch Point
                                                                                                                                                                                                                                                                                                                                                                                                                          1. Polypyrimidine Tract
                                                                                                                                                                                                                                                                                                                                                                                                                          2. Spliceosome Assembly
                                                                                                                                                                                                                                                                                                                                                                                                                            1. U1 snRNP Binding
                                                                                                                                                                                                                                                                                                                                                                                                                              1. U2AF Recruitment
                                                                                                                                                                                                                                                                                                                                                                                                                                1. U2 snRNP Binding
                                                                                                                                                                                                                                                                                                                                                                                                                                  1. U4/U6•U5 tri-snRNP
                                                                                                                                                                                                                                                                                                                                                                                                                                  2. Splicing Mechanism
                                                                                                                                                                                                                                                                                                                                                                                                                                    1. Two-Step Transesterification
                                                                                                                                                                                                                                                                                                                                                                                                                                      1. Lariat Intermediate
                                                                                                                                                                                                                                                                                                                                                                                                                                        1. Exon Ligation
                                                                                                                                                                                                                                                                                                                                                                                                                                        2. Alternative Splicing
                                                                                                                                                                                                                                                                                                                                                                                                                                          1. Exon Skipping
                                                                                                                                                                                                                                                                                                                                                                                                                                            1. Intron Retention
                                                                                                                                                                                                                                                                                                                                                                                                                                              1. Alternative 5' or 3' Sites
                                                                                                                                                                                                                                                                                                                                                                                                                                                1. Mutually Exclusive Exons
                                                                                                                                                                                                                                                                                                                                                                                                                                              2. RNA Editing
                                                                                                                                                                                                                                                                                                                                                                                                                                                1. C-to-U Editing
                                                                                                                                                                                                                                                                                                                                                                                                                                                  1. APOBEC Enzymes
                                                                                                                                                                                                                                                                                                                                                                                                                                                    1. Apolipoprotein B Editing
                                                                                                                                                                                                                                                                                                                                                                                                                                                    2. A-to-I Editing
                                                                                                                                                                                                                                                                                                                                                                                                                                                      1. ADAR Enzymes
                                                                                                                                                                                                                                                                                                                                                                                                                                                        1. Double-Strand RNA Substrates
                                                                                                                                                                                                                                                                                                                                                                                                                                                        2. Functional Consequences
                                                                                                                                                                                                                                                                                                                                                                                                                                                          1. Amino Acid Changes
                                                                                                                                                                                                                                                                                                                                                                                                                                                            1. Splice Site Creation
                                                                                                                                                                                                                                                                                                                                                                                                                                                              1. miRNA Target Sites