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• W2283702912 abstract "Complementary biochemical and genetic analyses reveal that SUMOylation of the six subunits of the MCM2–7 DNA helicase inhibits CMG formation, thereby negatively regulating DNA replication initiation in budding yeast. 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." @default.
• W2283702912 created "2016-06-24" @default.
• W2283702912 creator A5033457775 @default.
• W2283702912 creator A5090570063 @default.
• W2283702912 date "2016-02-08" @default.
• W2283702912 modified "2023-10-12" @default.
• W2283702912 title "A new MCM modification cycle regulates DNA replication initiation" @default.
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• W2283702912 doi "https://doi.org/10.1038/nsmb.3173" @default.
• W2283702912 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4823995" @default.
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• W2283702912 hasPublicationYear "2016" @default.
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