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Title: Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation

The CMG helicase is composed of Cdc45, Mcm2–7 and GINS. Here we report the structure of the Saccharomyces cerevisiae CMG, determined by cryo-EM at a resolution of 3.7–4.8 Å. The structure reveals that GINS and Cdc45 scaffold the N tier of the helicase while enabling motion of the AAA+ C tier. CMG exists in two alternating conformations, compact and extended, thus suggesting that the helicase moves like an inchworm. The N-terminal regions of Mcm2–7, braced by Cdc45–GINS, form a rigid platform upon which the AAA+ C domains make longitudinal motions, nodding up and down like an oil-rig pumpjack attached to a stable platform. The Mcm ring is remodeled in CMG relative to the inactive Mcm2–7 double hexamer. In addition, the Mcm5 winged-helix domain is inserted into the central channel, thus blocking entry of double-stranded DNA and supporting a steric-exclusion DNA-unwinding model.
Authors:
 [1] ;  [2] ;  [2] ;  [3] ;  [4] ;  [3] ;  [1]
  1. Stony Brook Univ., NY (United States). Department of Biochemistry & Cell Biology; Brookhaven National Lab. (BNL), Upton, NY (United States). Biology Department
  2. Brookhaven National Lab. (BNL), Upton, NY (United States). Biology Department
  3. Rockefeller Univ., New York, NY (United States). DNA Replication Laboratory and Howard Hughes Medical Institute
  4. University of Texas Medical School at Houston, Houston, Texas (United States). Department of Pathology and Laboratory Medicine
Publication Date:
Report Number(s):
BNL-111966-2016-JA
Journal ID: ISSN 1545-9993
Grant/Contract Number:
SC0012704
Type:
Accepted Manuscript
Journal Name:
Nature Structural & Molecular Biology
Additional Journal Information:
Journal Volume: 23; Journal Issue: 3; Journal ID: ISSN 1545-9993
Publisher:
Nature Publishing Group
Research Org:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org:
USDOE; National Institute of Health
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CMG; helicase; cryo-electron microscopy; replication; DNA translocation; strand exclusion
OSTI Identifier:
1335412