The corepressor silencing mediator for retinoid and thyroid hormone receptor facilitates cellular recovery from DNA double-strand breaks.
Cells are frequently challenged by DNA double-strand breaks (DSB) that threaten their normal function and survival. In mammalian cells, the repair of DSBs is predominantly mediated by the DNA-dependent protein kinase (DNA-PK) complex. We unexpectedly found that the corepressor silencing mediator for retinoid and thyroid hormone receptor (SMRT) associates with the DNA-PK repair complex. The SMRT/histone deacetylase 3 complex is required for the transcriptional repressive property of the Ku70 subunit of the repair complex. Moreover, SMRT, but not the related Nuclear Receptor Corepressor, is required for cellular recovery from DNA DSBs induced by ionizing radiation or DNA damage-inducing drugs. Thus, the corepressor SMRT plays a novel and critical role in the cellular response to DSBs.
Yu
Jiujiu
J
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6149, USA.
Palmer
Christine
C
Alenghat
Theresa
T
Li
Yun
Y
Kao
Gary
G
Lazar
Mitchell A
MA
D034961:Antigens, Nuclear / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013379:Substrate Specificity; D015533:Transcriptional Activation; D014162:Transfection; D000099186:Histone Deacetylase 3
D034961:Antigens, Nuclear; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D000072200:Ku Autoantigen; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C539127:NCOR1 protein, human; C539130:NCOR2 protein, human; C000606509:Xrcc6 protein, human