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CMG-Pol epsilon dynamics suggests a mechanism for the establishment of leading-strand synthesis in the eukaryotic replisome.

Authors :
Zhou JC
Janska A
Goswami P
Renault L
Abid Ali F
Kotecha A
Diffley JFX
Costa A
Source :
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Apr 18; Vol. 114 (16), pp. 4141-4146. Date of Electronic Publication: 2017 Apr 03.
Publication Year :
2017

Abstract

The replisome unwinds and synthesizes DNA for genome duplication. In eukaryotes, the Cdc45-MCM-GINS (CMG) helicase and the leading-strand polymerase, Pol epsilon, form a stable assembly. The mechanism for coupling DNA unwinding with synthesis is starting to be elucidated, however the architecture and dynamics of the replication fork remain only partially understood, preventing a molecular understanding of chromosome replication. To address this issue, we conducted a systematic single-particle EM study on multiple permutations of the reconstituted CMG-Pol epsilon assembly. Pol epsilon contains two flexibly tethered lobes. The noncatalytic lobe is anchored to the motor of the helicase, whereas the polymerization domain extends toward the side of the helicase. We observe two alternate configurations of the DNA synthesis domain in the CMG-bound Pol epsilon. We propose that this conformational switch might control DNA template engagement and release, modulating replisome progression.<br />Competing Interests: The authors declare no conflict of interest.

Details

Language :
English
ISSN :
1091-6490
Volume :
114
Issue :
16
Database :
MEDLINE
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
28373564
Full Text :
https://doi.org/10.1073/pnas.1700530114