A new MCM modification cycle regulates DNA replication initiation

Nat Struct Mol Biol. 2016 Mar;23(3):209-16. doi: 10.1038/nsmb.3173. Epub 2016 Feb 8.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle
  • DNA Replication*
  • Gene Expression Regulation, Fungal*
  • Minichromosome Maintenance Proteins / metabolism*
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / physiology
  • Sumoylation

Substances

  • Minichromosome Maintenance Proteins