A new MCM modification cycle regulates DNA replication initiation Journal Article


Authors: Wei, L.; Zhao, X.
Article Title: A new MCM modification cycle regulates DNA replication initiation
Abstract: The MCM DNA helicase is a central regulatory target during genome replication. MCM is kept inactive during G1, and it initiates replication after being activated in S phase. During this transition, the only known chemical change to MCM is the gain of multisite phosphorylation that promotes cofactor recruitment. Because replication initiation is intimately linked to multiple biological cues, additional changes to MCM can provide further regulatory points. Here, we describe a yeast MCM SUMOylation cycle that regulates replication. MCM subunits undergo SUMOylation upon loading at origins in G1 before MCM phosphorylation. MCM SUMOylation levels then decline as MCM phosphorylation levels rise, thus suggesting an inhibitory role of MCM SUMOylation during replication. Indeed, increasing MCM SUMOylation impairs replication initiation, partly through promoting the recruitment of a phosphatase that decreases MCM phosphorylation and activation. We propose that MCM SUMOylation counterbalances kinase-based regulation, thus ensuring accurate control of replication initiation. © 2016 Nature America, Inc.
Journal Title: Nature Structural and Molecular Biology
Volume: 23
Issue: 3
ISSN: 1545-9993
Publisher: Nature Publishing Group  
Date Published: 2016-03-01
Start Page: 209
End Page: 216
Language: English
DOI: 10.1038/nsmb.3173
PROVIDER: scopus
PUBMED: 26854664
PMCID: PMC4823995
DOI/URL:
Notes: Article -- Export Date: 4 April 2016 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Xiaolan Zhao
    77 Zhao
  2. Lei   Wei
    11 Wei