The Eukaryotic Replisome: a Guide to Protein Structure and Function (eBook)

Stuart MacNeill (Herausgeber)

eBook Download: PDF

2012 | 2012
VIII, 348 Seiten
Springer Netherland (Verlag)
978-94-007-4572-8 (ISBN)

Infos

High-fidelity chromosomal DNA replication underpins all life on the planet. In humans, there are clear links between chromosome replication defects and genome instability, genetic disease and cancer, making a detailed understanding of the molecular mechanisms of genome duplication vital for future advances in diagnosis and treatment. Building on recent exciting advances in protein structure determination, the book will take the reader on a guided journey through the intricate molecular machinery of eukaryotic chromosome replication and provide an invaluable source of information, ideas and inspiration for all those with an interest in chromosome replication, whether from a basic science, translational biology and medical research perspective.

Inhalt

Preface 1. Composition and dynamics of the eukaryotic replisome: a brief overview; Stuart A. MacNeill1.1 Introduction1.2 Replication origins and the origin recognition complex1.3 Formation of the pre-RC at origins1.4 The replisome progression complex1.5 The replicative polymerases1.6 Sliding clamp and clamp loader complexes1.7 Okazaki fragment processing1.8 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 systems1.9 ConclusionsAcknowledgementsReferences2. Evolutionary diversification of eukaryotic DNA replication machinery; Stephen J. Aves, Yuan Liu and Thomas A. Richards2.1 Introduction2.2 Eukaryotic diversity2.3 Conservation of replisome proteins2.4 Indispensable replisome proteins2.5 Replisome proteins present in all eukaryotic supergroups2.6 Replisome proteins not present in all supergroups2.7 A complex ancestral replisome2.8 ConclusionsReferences3. The origin recognition complex: a biochemical and structural view; Huilin Li and Bruce Stillman3.1 Introduction3.2 The S. cerevisiae ORC3.3 The S. pombe ORC3.4 The D. melanogaster ORC3.5 The H. sapiens ORC3.6 Future perspectivesAcknowledgementsReferences4. Archaeal Orc1/Cdc6 Proteins; Stephen D. Bell4.1 Introduction4.2 Origins of DNA replication in the Archaea4.3 Orc1/Cdc6 Structure4.4 Structures of Orc1/Cdc6 bound to DNA4.5 Beyond binding origins – what do Orc1/Cdc6s do?AcknowledgementsReferences5. Cdt1 and Geminin in DNA replication initiation; Christophe Caillat and Anastassis Perrakis5.1 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 differentiation5.3 The structure of Geminin   5.3.1 The N-terminal domain    5.3.2 The coiled-coil domain5.4 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 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 ConclusionsReferences6. 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 ConclusionsReferences7. 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 AcknowledgementsReferences8. 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 prospectsAcknowledgmentsReferences9. The Pol α-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 α   9.3.1 Catalytic activity   9.3.2 Structure of the B subunit and its interaction with Pol α9.4 Towards a concerted mechanism for primer synthesis by the Pol α-primase complex9.5 OutlookReferences10. 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 RPAAcknowledgementsReferences11. 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 References12. 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 p50p66N   12.3.2 p50p66 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 prospectsReferences13. DNA polymerase ε; Matthew Hogg and Erik Johansson13.1 Introduction13.2 Structure of Pol ε subunits   13.2.1 Pol2   13.2.2 Dpb2   13.2.3 Dpb3/Dpb4 dimer13.3 Structure of Pol ε 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 remarksAcknowledgementsReferences14. 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 ConclusionsReferences15. 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 remarksAcknowledgementsReferences16. 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 5ʹ-strand interactions   16.3.4 Protein substrate complex 5ʹ-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 intermediatesAcknowledgementsReferences17. 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

Produkt-Details

• Erscheint lt. Verlag: 23.8.2012
• Reihe/Serie: Subcellular Biochemistry
• Reihe/Serie: Subcellular Biochemistry
• Zusatzinfo: VIII, 348 p.
• Verlagsort: Dordrecht
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Onkologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Biochemie
• Themenwelt: Technik
• Schlagworte: chromosome replication • DNA Replication • genome duplication • Protein Structure • replisome
• ISBN-10: 94-007-4572-9 / 9400745729
• ISBN-13: 978-94-007-4572-8 / 9789400745728