title: 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 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, inhibition in the activity of the core mitotic regulator CDK1, either by pharmacologic inhibition or siRNA attenuation, enhances MDC1-γH2AX colocalization in mitosis. Our findings offer key new insights into how DDR is controlled during mitosis.
authors.affiliation: Department of Medicine, Stony Brook University School of Medicine, Stony Brook, New York 11794-8160, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.forename: W Brian
authors.initials: WB
authors.lastname: Dalton
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D045325:HCT116 Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008938:Mitosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C468783:H2AX protein, human; D006657:Histones; C413163:MDC1 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D016203:CDC2 Protein Kinase