The Eukaryotic Replisome: a Guide to Protein Structure and Function

winged helix domains   5.4.3 The recruitment of Cdt1 on chromatin5.5 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 switch5.7 ConclusionsReferences

6. MCM structure and mechanics: what we have learned from archaeal MCM: Ian M. Slaymaker and Xiaojiang S. Chen6.1 Introduction6.2 Complex organization: Hexamers and double hexamers6.3 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 domain6.5 Inter- and intra-subunit communication6.6 Higher-order MCM oligomers 6.7 ConclusionsReferences

7. The Eukaryotic Mcm2-7 Replicative Helicase; Sriram Vijayraghavan and Anthony Schwacha7.1 Introduction 7.2 The 'Mcm problem' and nonequivalent ATPase active sites7.3 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 exclusive7.4 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 gate7.5 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 elongation7. 6 Speculative model for Mcm2-7 function AcknowledgementsReferences

8. The GINS complex: structure and function; Katsuhiko Kamada8.1 Introduction8.2 Discovery of GINS8.3 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 complex8.4 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 action8.5 Archaeal GINS   8.5.1 Structure and evolution   8.5.2 Biological functions of archaeal GINS8.6 Conclusions and prospectsAcknowledgmentsReferences

9. The Pol a-primase complex; Luca Pellegrini9.1 Introduction9.2 Primase   9.2.1 Prim fold of the catalytic subunit   9.2.2 The archaeal/eukaryotic primase is an iron-sulfur protein9.3 DNA polymerase a   9.3.1 Catalytic activity   9.3.2 Structure of the B subunit and its interaction with Pol a9.4 Towards a concerted mechanism for primer synthesis by the Pol a-primase complex9.5 OutlookReferences

10. The structure and function of replication protein A in DNA replication; Aishwarya Prakash and Gloria E. O. Borgstahl10.1 Introduction 10.2 Evolution of RPA10.3 RPA structure10.4 Interactions of RPA with single-stranded DNA10.5 DNA structure and requirement for RPA 10.6 RPA binding to non-canonical DNA structures10.7 RPA binding to damaged DNA10.8 Role in recruiting proteins to the replication fork10.9 Concluding remarks - future research on RPAAcknowledgementsReferences

11. Structural biology of replication initiation factor Mcm10; Wenyue Du, Melissa E. Stauffer and Brandt F. Eichman11.1 Replication initiation11.2 Role of Mcm10 in replication11.3 Overall architecture11.4 Mcm10 domain structure   11.4.1 Mcm10-NTD   11.4.2 Mcm10-ID   11.4.3 Mcm10-CTD11.5 Implications of modular architecture for function11.6 Summary and future perspectives References

12. Structure and function of eukaryotic DNA polymerase d; Tahir H. Tahirov12.1 Introduction12.2 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 p50Ÿp66N   12.3.2 p50Ÿp66 Interactions    12.3.3 Functional studies   12.3.4 Crystal structure of p66.PCNA12.4 D-subunit   12.4.1 D-subunit structure and inter-subunit interactions   12.4.2 D-subunit function12.5 Conclusions and prospectsReferences

13. DNA polymerase e; Matthew Hogg and Erik Johansson13.1 Introduction13.2 Structure of Pol e subunits   13.2.1 Pol2   13.2.2 Dpb2   13.2.3 Dpb3/Dpb4 dimer13.3 Structure of Pol e holoenzyme13.4 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 discrimination13.6 Concluding remarksAcknowledgementsReferences

14. The RFC clamp loader: structure and function; Nina Y. Yao and Mike O'Donnell14.1 Overview of clamp loaders and sliding clamps14.2 Clamp loader structure 14.3 RFC clamp loader interaction with DNA14.4 ATP binding and opening of the clamp14.5 ATP hydrolysis and closing of the clamp14.6 Clamp loaders also unload clamps after replication14.7 Alternative RFCs14.8 ConclusionsReferences

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 Washington15.1 Introduction15.2 Structure of PCNA15.3 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 issues15.4 Structures of mutant PCNA proteins15.5 Structures of post-translationally modified PCNA   15.5.1 Structure of ubiquitin-modified PCNA   15.5.2 Structure of SUMO-modified PCNA15.6 Concluding remarksAcknowledgementsReferences

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 Shen16.1 Introduction16.2 Biochemical activity16.3 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 Modifications16.5 Handoff of DNA intermediatesAcknowledgementsReferences

17. DNA ligase I, the replicative DNA ligase; Timothy R.L. Howes, Alan E. Tomkinson17.1 Introduction17.2 Eukaryotic DNA ligase genes17.3 DNA ligase I: molecular genetics and cell biology17.4 DNA ligase I protein: structure and function17.5 DNA ligase I: protein interactions17.6 Concluding remarksReferences