The Eukaryotic Replisome: A Guide to Protein Structure and Function

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 regu