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• W2111837850 abstract "Several regulatory proteins control cell cycle progression. These include Emi1, an anaphase-promoting complex (APC) inhibitor whose destruction controls progression through mitosis to G1, and p21 WAF1 , a cyclin-dependent kinase (CDK) inhibitor activated by DNA damage. We have analyzed the role of p21 WAF1 in G2-M phase checkpoint control and in prevention of polyploidy after DNA damage. After DNA damage, p21 +/+ cells stably arrest in G2, whereas p21 −/− cells ultimately progress into mitosis. We report that p21 down-regulates Emi1 in cells arrested in G2 by DNA damage. This down-regulation contributes to APC activation and results in the degradation of key mitotic proteins including cyclins A2 and B1 in p21 +/+ cells. Inactivation of APC in irradiated p21 +/+ cells can overcome the G2 arrest. siRNA-mediated Emi1 down-regulation prevents irradiated p21 −/− cells from entering mitosis, whereas concomitant down-regulation of APC activity counteracts this effect. Our results demonstrate that Emi1 down-regulation and APC activation leads to stable p21-dependent G2 arrest after DNA damage. This is the first demonstration that Emi1 regulation plays a role in the G2 DNA damage checkpoint. Further, our work identifies a new p21-dependent mechanism to maintain G2 arrest after DNA damage." @default.
• W2111837850 created "2016-06-24" @default.
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• W2111837850 date "2009-04-01" @default.
• W2111837850 modified "2023-10-09" @default.
• W2111837850 title "DNA Damage Triggers p21^WAF1-dependent Emi1 Down-Regulation That Maintains G2 Arrest" @default.
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• W2111837850 doi "https://doi.org/10.1091/mbc.e08-08-0818" @default.
• W2111837850 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2663934" @default.
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• W2111837850 hasPublicationYear "2009" @default.
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