Subcellular Biochemistry

Preface 1. Composition and dynamics of the eukaryotic replisome: a brief overview; Stuart A. MacNeill 1.1 Introduction 1.2 Replication origins and the origin recognition complex 1.3 Formation of the pre-RC at origins 1.4 The replisome progression complex 1.5 The replicative polymerases 1.6 Sliding clamp and clamp loader complexes 1.7 Okazaki fragment processing 1.8 Model systems for the studying eukaryotic replication 1.8.1 SV40 1.8.2 Yeast 1.8.3 Xenopus 1.8.4 Archaea 1.8.5 Other model systems 1.9 Conclusions Acknowledgements References 2. Evolutionary diversification of eukaryotic DNA replication machinery; Stephen J. Aves, Yuan Liu and Thomas A. Richards 2.1 Introduction 2.2 Eukaryotic diversity 2.3 Conservation of replisome proteins 2.4 Indispensable replisome proteins 2.5 Replisome proteins present in all eukaryotic supergroups 2.6 Replisome proteins not present in all supergroups 2.7 A complex ancestral replisome 2.8 Conclusions References 3. The origin recognition complex: a biochemical and structural view; Huilin Li and Bruce Stillman 3.1 Introduction 3.2 The S. cerevisiae ORC 3.3 The S. pombe ORC 3.4 The D. melanogaster ORC 3.5 The H. sapiens ORC 3.6 Future perspectives Acknowledgements References 4. Archaeal Orc1/Cdc6 Proteins; Stephen D. Bell 4.1 Introduction 4.2 Origins of DNA replication in the Archaea 4.3 Orc1/Cdc6 Structure 4.4 Structures of Orc1/Cdc6 bound to DNA 4.5 Beyond binding origins -- what do Orc1/Cdc6s do?Acknowledgements References 5. Cdt1 and Geminin in DNA replication initiation; Christophe Caillat and Anastassis Perrakis 5.1 Cdt1 and Geminin: a functional preview5.2 The multiple faces of Geminin 5.2.1 Geminin functions in replication licensing 5.2.2 Geminin in the cell cycle 5.2.3 Geminin in cell differentiation 5.3 The structure of Geminin 5.3.1 The N-terminal domain 5.3.2 The coiled-coil domain 5.4 The structure of Cdt1 5.4.1 The N-terminal domain is highly regulated 5.4.2 The structurally conserved winged helix domains 5.4.3 The recruitment of Cdt1 on chromatin 5.5 The Cdt1-Geminin complex 5.5.1 The primary and secondary interfaces 5.5.2 The tertiary interface 5.5.3 Conformational change of the N-terminal domain? 5.6 Models for a Cdt1-Geminin molecular switch 5.7 Conclusions References 6. MCM structure and mechanics: what we have learned from archaeal MCM: Ian M. Slaymaker and Xiaojiang S. Chen 6.1 Introduction 6.2 Complex organization: Hexamers and double hexamers 6.3 Helicase activity 6.3.1 Steric exclusion 6.3.2 Ploughshare 6.3.3 LTag looping model (or strand exclusion) 6.3.4 Rotary pump 6.4 Domains and features of an MCM subunit 6.4.1 N domain 6.4.2 C domain 6.4.2.1 ATP binding pocket 6.4.2.2 Hairpins, helices and inserts 6.4.2.3 Winged helix domain 6.5 Inter- and intra-subunit communication 6.6 Higher-order MCM oligomers 6.7 Conclusions References 7. The Eukaryotic Mcm2-7 Replicative Helicase; Sriram Vijayraghavan and Anthony Schwacha 7.1 Introduction 7.2 The 'Mcm problem' and nonequivalent ATPase active sites 7.3 Discovery of Mcm2-7 helicase activity and the Mcm2/5 gate 7.3.1 Differences in circular ssDNA binding between Mcm2-7 and Mcm467 7.3.2 An in vitro condition that 'closes' Mcm2-7 stimulates its helicase activity 7.3.3 The Mcm2/5 'gate' model -- the open conformation and DNA unwinding are mutually exclusive 7.4 The CMG complex 7.4.1 Discovery of the CMG complex 7.4.2 CMG structure -- Cdc45 and GINS close the Mcm2/5 gate 7.4.3 Possible regulation of the Mcm2/5 gate 7.5 How does Mcm2-7 unwind DNA? 7.5.1 Mcm2-7 loads as double hexamers onto dsDNA 7.5.2 Single-molecule studies eliminate the dsDNA pump model for elongation 7. 6 Speculative model for Mcm2-7 function Acknowledgements References 8. The GINS complex: structure and function; Katsuhiko Kamada 8.1 Introduction 8.2 Discovery of GINS 8.3 GINS functions 8.3.1 Replication initiation in the budding yeast 8.3.2 Replication initiation in the fission yeast 8.3.3 Replication initiation in higher eukaryotes 8.3.4 GINS in the replication progression complex 8.4 Structure of GINS 8.4.1 Overall structure 8.4.2 Two structural domains in all subunits 8.4.3 Functional interface of the GINS complex 8.4.4 GINS and the CMG complex 8.4.5 EM images and DNA clamping action 8.5 Archaeal GINS 8.5.1 Structure and evolution 8.5.2 Biological functions of archaeal GINS 8.6 Conclusions and prospects Acknowledgments References 9. The Pol I -primase complex; Luca Pellegrini 9.1 Introduction 9.2 Primase 9.2.1 Prim fold of the catalytic subunit 9.2.2 The archaeal/eukaryotic primase is an iron-sulfur protein 9.3 DNA polymerase I 9.3.1 Catalytic activity 9.3.2 Structure of the B subunit and its interaction with Pol I 9.4 Towards a concerted mechanism for primer synthesis by the Pol I -primase complex 9.5 Outlook References 10. The structure and function of replication protein A in DNA replication; Aishwarya Prakash and Gloria E. O. Borgstahl 10.1 Introduction 10.2 Evolution of RPA 10.3 RPA structure 10.4 Interactions of RPA with single-stranded DNA 10.5 DNA structure and requirement for RPA 10.6 RPA binding to non-canonical DNA structures 10.7 RPA binding to damaged DNA 10.8 Role in recruiting proteins to the replication fork 10.9 Concluding remarks -- future research on RPA Acknowledgements References 11. Structural biology of replication initiation factor Mcm10; Wenyue Du, Melissa E. Stauffer and Brandt F. Eichman 11.1 Replication initiation 11.2 Role of Mcm10 in replication 11.3 Overall architecture 11.4 Mcm10 domain structure 11.4.1 Mcm10-NTD 11.4.2 Mcm10-ID 11.4.3 Mcm10-CTD 11.5 Implications of modular architecture for function 11.6 Summary and future perspectives References12. Structure and function of eukaryotic DNA polymerase d; Tahir H. Tahirov 12.1 Introduction 12.2 Catalytic subunit (A-subunit) 12.2.1 Crystal structure of catalytic core 12.2.2 Cancer-causing mutations 12.2.3 C-terminal domain 12.2.4 Similarities between C-terminal domains of Pol d and Pol z 12.3 B- and C-subunits 12.3.1 Crystal structure of p50 p66N 12.3.2 p50 p66 Interactions 12.3.3 Functional studies 12.3.4 Crystal structure of p66*PCNA 12.4 D-subunit 12.4.1 D-subunit structure and inter-subunit interactions 12.4.2 D-subunit function 12.5 Conclusions and prospects References 13. DNA polymerase I ; Matthew Hogg and Erik Johansson 13.1 Introduction 13.2 Structure of Pol I subunits 13.2.1 Pol2 13.2.2 Dpb2 13.2.3 Dpb3/Dpb4 dimer 13.3 Structure of Pol I holoenzyme 13.4 Higher order structures 13.4.1 Initiation of DNA replication 13.4.2 Role at the replication fork 13.4.3 PCNA 13.4.4 Checkpoint activation in S phase 13.5 Ribose vs deoxyribose discrimination 13.6 Concluding remarks Acknowledgements References 14. The RFC clamp loader: structure and function; Nina Y. Yao and Mike O'Donnell 14.1 Overview of clamp loaders and sliding clamps 14.2 Clamp loader structure 14.3 RFC clamp loader interaction with DNA 14.4 ATP binding and opening of the clamp 14.5 ATP hydrolysis and closing of the clamp 14.6 Clamp loaders also unload clamps after replication 14.7 Alternative RFCs 14.8 Conclusions References 15. PCNA structure and function: insights from structures of PCNA complexes and post-translationally modified PCNA; Lynne M. Dieckman, Bret D. Freudenthal and M. Todd Washington 15.1 Introduction 15.2 Structure of PCNA 15.3 Structures of PCNA complexes 15.3.1 Structures of PCNA bound to PIP peptides 15.3.2 Structures of PCNA bound to full-length proteins 15.3.3 Low resolution structures of PCNA complexes 15.3.4 Unresolved issues 15.4 Structures of mutant PCNA proteins 15.5 Structures of post-translationally modified PCNA 15.5.1 Structure of ubiquitin-modified PCNA 15.5.2 Structure of SUMO-modified PCNA 15.6 Concluding remarks Acknowledgements References 16. The wonders of Flap Endonucleases: structure, function, mechanism and regulation; L. David Finger, John M. Atack, Susan Tsutakawa, Scott Classen, John Tainer, Jane Grasby, Binghui Shen 16.1 Introduction 16.2 Biochemical activity 16.3 FEN structure and substrate recognition 16.3.1 Free protein 16.3.2 Protein-product and protein-substrate complexes 16.3.3 Protein product complex 5'-strand interactions 16.3.4 Protein substrate complex 5'-flap strand interactions 16.3.5 Bind-then-thread or bind-then-clamp 16.3.6 Scissile phosphate placement: the double nucleotide unpairing trap (DoNUT) 16.3.7 Cleavage of the scissile phosphate diester: active site structure 16.4 Regulation of FEN1 Activity 16.4.1 Protein-protein interactions 16.4.1.1 PCNA 16.4.1.2 RecQ helicase family interactions 16.4.2 Post-translational Modifications 16.5 Handoff of DNA intermediates Acknowledgements References17. DNA ligase I, the replicative DNA ligase; Timothy R.L. Howes, Alan E. Tomkinson 17.1 Introduction 17.2 Eukaryotic DNA ligase genes 17.3 DNA ligase I: molecular genetics and cell biology 17.4 DNA ligase I protein: structure and function 17.5 DNA ligase I: protein interactions 17.6 Concluding remarks References