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- W2020704295 abstract "Progression through the mammalian cell division cycle is regulated by the sequential activation of cyclin-dependent kinases, CDKs, at specific phases of the cell cycle. Cyclin A-CDK2 and cyclin A-CDK1 phosphorylate nuclear substrates during S and G2 phases, respectfully. However, the DNA helicase complex, MCM2-7, is loaded onto the origin of replications in G1, prior to the normally scheduled induction of cyclin A. It has previously been shown that cyclin A-CDKs phosphorylate MCM2 and MCM4 in vitro, thereby diminishing helicase activity. Thus, in this study we hypothesize that, in vivo, cyclin A-CDK activity during G1 would result in an inhibition of progression into the S phase. To test this, we establish an in vivo method of inducing cyclin A-CDK activity in G1 phase and observe that activation of cyclin A-CDK, but not cyclin E-CDK complexes, inhibit DNA synthesis without affecting other G1 events such as cyclin D synthesis, E2F activation and cdc6 loading onto chromatin. We further report that the mechanism of this S phase inhibition occurs, at least in part, through impaired loading of MCM onto chromatin, presumably due to decreased levels of cdt1 and premature phosphorylation of MCM by cyclin A-CDK. In addition to providing in vivo confirmation of in vitro predictions regarding cyclin A-CDK phosphorylation of the MCM complex, our results provide insight into the cellular effects of unscheduled cyclin A-CDK activity in mammalian cells." @default.
- W2020704295 created "2016-06-24" @default.
- W2020704295 creator A5005736184 @default.
- W2020704295 creator A5012462653 @default.
- W2020704295 creator A5062015710 @default.
- W2020704295 date "2008-07-15" @default.
- W2020704295 modified "2023-10-18" @default.
- W2020704295 title "Cyclin A-CDK activity during G1 phase impairs MCM chromatin loading and inhibits DNA synthesis in mammalian cells" @default.
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- W2020704295 doi "https://doi.org/10.4161/cc.7.14.6270" @default.
- W2020704295 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18635963" @default.
- W2020704295 hasPublicationYear "2008" @default.
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