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CDK1 regulates mediator of DNA damage checkpoint 1 during mitotic DNA damage.

ABSTRACT: Cells engage sophisticated programs of DNA damage response (DDR) and repair to guard against genetic mutations. Although there is significant knowledge concerning DDR in interphase cells, much less is known about these processes in mitosis. Direct interaction between MDC1, a master DDR organizer, and a marker of DNA damage, histone ?H2AX, is required to trigger robust repair. Here we show that the DNA damage-induced interaction between MDC1 and ?H2AX is attenuated in mitosis. Furthermore, inhibition in the activity of the core mitotic regulator CDK1, either by pharmacologic inhibition or siRNA attenuation, enhances MDC1-?H2AX colocalization in mitosis. Our findings offer key new insights into how DDR is controlled during mitosis.

SUBMITTER: Yu B

PROVIDER: S-EPMC3488166 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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CDK1 regulates mediator of DNA damage checkpoint 1 during mitotic DNA damage.

Yu Bing B Dalton W Brian WB Yang Vincent W VW

Cancer research 20120907 21

Cells engage sophisticated programs of DNA damage response (DDR) and repair to guard against genetic mutations. Although there is significant knowledge concerning DDR in interphase cells, much less is known about these processes in mitosis. Direct interaction between MDC1, a master DDR organizer, and a marker of DNA damage, histone γH2AX, is required to trigger robust repair. Here we show that the DNA damage-induced interaction between MDC1 and γH2AX is attenuated in mitosis. Furthermore, inhibi ...[more]

PMID: 22962268

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