Mediator of DNA Damage Checkpoint Protein 1 Regulates BRCA1 Localization and Phosphorylation in DNA Damage Checkpoint Control
Copyright policy )Mediator of DNA Damage Checkpoint Protein 1 Regulates BRCA1 Localization and Phosphorylation in DNA Damage Checkpoint Control
BRCA1 is a tumor suppressor involved in DNA repair and damage-induced checkpoint controls. In response to DNA damage, BRCA1 relocalizes to nuclear foci at the sites of DNA lesions. However, little is known about the regulation of BRCA1 relocalization following DNA damage. Here we show that mediator of DNA damage checkpoint protein 1 (MDC1), previously named NFBD1 or Kiaa0170, is a proximate mediator of DNA damage responses that regulates BRCA1 function. MDC1 regulates ataxia-telangiectasia-mutated (ATM)-dependent phosphorylation events at the site of DNA damage. Importantly down-regulation of MDC1 abolishes the relocalization and hyperphosphorylation of BRCA1 following DNA damage, which coincides with defective G(2)/M checkpoint control in response to DNA damage. Taken together these data suggest that MDC1 regulates BRCA1 function in DNA damage checkpoint control.
- Mayo Clinic United States
DNA, Complementary, Dose-Response Relationship, Drug, BRCA1 Protein, Cell Cycle, Down-Regulation, Nuclear Proteins, Cell Cycle Proteins, Dose-Response Relationship, Radiation, Ataxia Telangiectasia Mutated Proteins, DNA-Binding Proteins, Microscopy, Fluorescence, Checkpoint Kinase 1, Humans, Phosphorylation, K562 Cells, Adaptor Proteins, Signal Transducing, DNA Damage, Glutathione Transferase, HeLa Cells, Plasmids
DNA, Complementary, Dose-Response Relationship, Drug, BRCA1 Protein, Cell Cycle, Down-Regulation, Nuclear Proteins, Cell Cycle Proteins, Dose-Response Relationship, Radiation, Ataxia Telangiectasia Mutated Proteins, DNA-Binding Proteins, Microscopy, Fluorescence, Checkpoint Kinase 1, Humans, Phosphorylation, K562 Cells, Adaptor Proteins, Signal Transducing, DNA Damage, Glutathione Transferase, HeLa Cells, Plasmids
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