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Title: The eukaryotic CMG helicase pumpjack and integration into the replisome

Journal Article · · Nucleus
 [1];  [2];  [3];  [4];  [3]
  1. Brookhaven National Lab. (BNL), Upton, NY (United States). Biology Dept.
  2. State Univ. of New York (SUNY), Stony Brook, NY (United States). Dept. of Biochemistry & Cell Biology
  3. Rockefeller Univ., New York, NY (United States). Howard Hughes Medical Inst. DNA Replication Lab.
  4. Brookhaven National Lab. (BNL), Upton, NY (United States). Biology Dept.; State Univ. of New York (SUNY), Stony Brook, NY (United States). Dept. of Biochemistry & Cell Biology

The eukaryotic replisome is a multiprotein machine that contains DNA polymerases, sliding clamps, helicase, and primase along with several factors that participate in cell cycle and checkpoint control. The detailed structure of the 11-subunit CMG helicase (Cdc45/Mcm2-7/GINS) has been solved recently by cryoEM single-particle 3D reconstruction and reveals pumpjack motions that imply an unexpected mechanism of DNA translocation. CMG is also the organizing center of the replisome. Recent in vitro reconstitution of leading and lagging strand DNA synthesis has enabled structural analysis of the replisome. By building the replisome in stages from pure proteins, single-particle EM studies have identified the overall architecture of the eukaryotic replisome. Suprisingly leading and lagging strand polymerases bind to opposite faces of the CMG helicase, unlike the long-held view that DNA polymerases are located in back of the helicase to act on the unwound strands.

Research Organization:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-98CH10886; NIH [GM111472, OD12272, GM115809]
OSTI ID:
1625101
Journal Information:
Nucleus, Vol. 7, Issue 2; ISSN 1949-1034
Publisher:
Taylor & FrancisCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 8 works
Citation information provided by
Web of Science

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Cited By (5)

RNA‐sequence‐based microRNA expression signature in breast cancer: tumor‐suppressive miR‐101‐5p regulates molecular pathogenesis journal December 2019
Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation journal January 2017
CMG–Pol epsilon dynamics suggests a mechanism for the establishment of leading-strand synthesis in the eukaryotic replisome journal April 2017
DNA polymerase δ proofreads errors made by DNA polymerase ε journal March 2020
E3 ubiquitin ligase Bre1 couples sister chromatid cohesion establishment to DNA replication in Saccharomyces cerevisiae journal October 2017

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