The corepressor silencing mediator for retinoid and thyroid hormone receptor facilitates cellular recovery from DNA double-strand breaks

Jiujiu Yu; Christine Palmer; Theresa Alenghat; Yun Li; Gary Kao; Mitchell A. Lazar

doi:10.1158/0008-5472.CAN-06-1902

The corepressor silencing mediator for retinoid and thyroid hormone receptor facilitates cellular recovery from DNA double-strand breaks

Jiujiu Yu, Christine Palmer, Theresa Alenghat, Yun Li, Gary Kao, Mitchell A. Lazar

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	9316-9322
Number of pages	7
Journal	Cancer Research
Volume	66
Issue number	18
DOIs	https://doi.org/10.1158/0008-5472.CAN-06-1902
State	Published - Sep 15 2006
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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abstract = "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.",

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AU - Yu, Jiujiu

AU - Palmer, Christine

AU - Alenghat, Theresa

AU - Li, Yun

AU - Kao, Gary

AU - Lazar, Mitchell A.

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AB - 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.

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The corepressor silencing mediator for retinoid and thyroid hormone receptor facilitates cellular recovery from DNA double-strand breaks

Abstract

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