The architecture of a eukaryotic replisome

Sun, Jingchuan; Yuan, Zuanning; Shi, Yi; Georgescu, Roxana E.; Chait, Brian T.; Li, Huilin; O'Donnell, Michael E.

doi:10.1038/nsmb.3113

Title: The architecture of a eukaryotic replisome

Journal Article · Mon Nov 02 00:00:00 EST 2015 · Nature Structural & Molecular Biology

DOI:https://doi.org/10.1038/nsmb.3113· OSTI ID:1257963

Sun, Jingchuan ^[1]; Yuan, Zuanning ^[1]; Shi, Yi ^[2]; Georgescu, Roxana E. ^[2]; Chait, Brian T. ^[2]; Li, Huilin ^[1]; O'Donnell, Michael E. ^[2]

Brookhaven National Lab. (BNL), Upton, NY (United States); Stony Brook Univ., Stony Brook, NY (United States)
Rockefeller Univ., New York, NY (United States)

At the eukaryotic DNA replication fork, it is widely believed that the Cdc45–Mcm2–7–GINS (CMG) helicase is positioned in front to unwind DNA and that DNA polymerases trail behind the helicase. Here we used single-particle EM to directly image a Saccharomyces cerevisiae replisome. Contrary to expectations, the leading strand Pol ε is positioned ahead of CMG helicase, whereas Ctf4 and the lagging-strand polymerase (Pol) α–primase are behind the helicase. This unexpected architecture indicates that the leading-strand DNA travels a long distance before reaching Pol ε, first threading through the Mcm2–7 ring and then making a U-turn at the bottom and reaching Pol ε at the top of CMG. Lastly, our work reveals an unexpected configuration of the eukaryotic replisome, suggests possible reasons for this architecture and provides a basis for further structural and biochemical replisome studies.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: SC00112704

OSTI ID:: 1257963

Report Number(s):: BNL-112308-2016-JA

Journal Information:: Nature Structural & Molecular Biology, Vol. 22, Issue 12; ISSN 1545-9993

Country of Publication:: United States

Language:: English

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Cited by: 130 works

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Histone chaperone networks shaping chromatin function Hammond, Colin M.; Strømme, Caroline B.; Huang, Hongda Nature Reviews Molecular Cell Biology, Vol. 18, Issue 3 https://doi.org/10.1038/nrm.2016.159	journal	January 2017
Quality control mechanisms exclude incorrect polymerases from the eukaryotic replication fork Schauer, Grant D.; O’Donnell, Michael E. Proceedings of the National Academy of Sciences, Vol. 114, Issue 4 https://doi.org/10.1073/pnas.1619748114	journal	January 2017
Cryo-EM structure of the replisome reveals multiple interactions coordinating DNA synthesis Kulczyk, Arkadiusz W.; Moeller, Arne; Meyer, Peter Proceedings of the National Academy of Sciences, Vol. 114, Issue 10 https://doi.org/10.1073/pnas.1701252114	journal	February 2017
DNA replication protein Cdc45 directly interacts with PCNA via its PIP box in Leishmania donovani and the Cdc45 PIP box is essential for cell survival Yadav, Aarti; Sharma, Varshni; Pal, Jyoti PLOS Pathogens, Vol. 16, Issue 5 https://doi.org/10.1371/journal.ppat.1008190	journal	May 2020
Recent advances in cohesin biology Rankin, Susannah; Dawson, Dean S. F1000Research, Vol. 5 https://doi.org/10.12688/f1000research.8881.1	journal	August 2016
Reconstitution of a eukaryotic replisome reveals the mechanism of asymmetric distribution of DNA polymerases Yurieva, Olga; O'Donnell, Mike Nucleus, Vol. 7, Issue 4 https://doi.org/10.1080/19491034.2016.1205774	journal	July 2016
CMG–Pol epsilon dynamics suggests a mechanism for the establishment of leading-strand synthesis in the eukaryotic replisome Zhou, Jin Chuan; Janska, Agnieszka; Goswami, Panchali Proceedings of the National Academy of Sciences, Vol. 114, Issue 16 https://doi.org/10.1073/pnas.1700530114	journal	April 2017

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