Molecular Themes in DNA Replication Book

Chapter 1. Introduction: conserved steps in eukaryotic DNA replication: Template; Origins; Origin recognition; Pre-initiation; Initiation; Elongation; Termination; Chromatid cohesion and segregation. Chapter 2. AAA and ATPases in loading replication factors: ORC and loading of Cdc6; Cdc6 and loading of MCMs; RFC and loading of PCNA. Chapter 3. Ring structures and six fold symmetry in replication: Helicases: MCMs; WRN, BLM etc; Clamps: PCNA; Rad9-Rad1-Hus1. Chapter 4: Polymerization mechanisms: Thermodynamics of polymerization; Structural insights into polymerization mechanisms; fidelity: Replicative polymerase error rates; Enhancing polymerase fidelity by protein interactions. Chapter 5. Molecular hand-off mechanisms in replication: Priming polymerization; Polymerase switches; Okazaki fragment processing: differential affinities for PCNA; Methylation and chromatin modification via molecular hand-off mediated through PCNA?; RPA in replication/repair. Chapter 6. Co-ordination of nucleases and helicases: Nucleases in replication: conservation of roles and mechanisms; Fen1 and Dna2 at Okazaki fragments; Stalled forks, helicases and nucleases - BLM, WRN, Exo1 and others. Chapter 7. The switch from replication to repair (and back): Monitoring DNA integrity; Stalled replication forks and replisome stability: impact of lesion type; Choosing the right polymerase through PCNA modification; Polymerase switching over lesions; Restarting stalled forks after repair. Chapter 8: Telomeres and the end replication problem: Structure and stability of telomeres; Telomerase: structural and drug inhibition studies; ALT pathways of telomere maintenance; Telomere length and telomere-specific sister chromatid exchange in replicative senescence. Keeping replicated chromatids together until mitosis: Topoisomerases and separating chromatids; SMC proteins, claspins and cohesions; Attaching chromatids to the mitotic spindle - the role of ORC. Chapter 10. Chromatin modification during replication: Chromatin context and replication patterns; Silenced loci and dormant origins; DNA methylation during replication; Histone modifications (methylation, acetylation, phosphorylation, ubiquitination - CAF1, SIRT1, SNF2/HDACs etc); Nucleosome positioning in relation to origins. Chapter 11. Mittochondrial DNA replication: Template: copy number, structure and origin; DNA pol gamma - mode of action; Accessory factors; Regulation - autonomous or integrated with cell cycle?; Co-ordination with damage sensing and repair. Chapter 12. Archaeal paradigms and parallels for eukaryotic DNA replication: Overview: comparison between archaeal and eukaryotic replication proteins and processes; Insights into priming from the structure of the primase core; Archaeal MCMs as a model for eukaryotic MCMs; Structure of the archaeal preRC and stabilization by GINS; Protein interactions with PCNA. Chapter 13. Drug targets in DNA replication: Nuclear replication: ORC, MCMs and GINS - markers or targets?; Geminin; PCNA (p21) and Ciz; Polymerases; Telomerase; Mitochondrial replication targets; Malaria and potential novel drug targets.