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Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C.

ABSTRACT: Disruption of the nucleotide excision repair (NER) pathway by mutations can cause xeroderma pigmentosum, a syndrome predisposing affected individuals to development of skin cancer. The xeroderma pigmentosum C (XPC) protein is essential for initiating global genome NER by recognizing the DNA lesion and recruiting downstream factors. Here we show that inhibition of the deacetylase and longevity factor SIRT1 impairs global genome NER through suppressing the transcription of XPC in a SIRT1 deacetylase-dependent manner. SIRT1 enhances XPC expression by reducing AKT-dependent nuclear localization of the transcription repressor of XPC. Finally, we show that SIRT1 levels are significantly reduced in human skin tumors from Caucasian patients, a population at highest risk. These findings suggest that SIRT1 acts as a tumor suppressor through its role in DNA repair.

SUBMITTER: Ming M

PROVIDER: S-EPMC3012476 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C.

Ming Mei M Shea Christopher R CR Guo Xiumei X Li Xiaoling X Soltani Keyoumars K Han Weinong W He Yu-Ying YY

Proceedings of the National Academy of Sciences of the United States of America 20101213 52

Disruption of the nucleotide excision repair (NER) pathway by mutations can cause xeroderma pigmentosum, a syndrome predisposing affected individuals to development of skin cancer. The xeroderma pigmentosum C (XPC) protein is essential for initiating global genome NER by recognizing the DNA lesion and recruiting downstream factors. Here we show that inhibition of the deacetylase and longevity factor SIRT1 impairs global genome NER through suppressing the transcription of XPC in a SIRT1 deacetyla ...[more]

PMID: 21149730

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Checkpoint kinase ATR promotes nucleotide excision repair of UV-induced DNA damage via physical interaction with xeroderma pigmentosum group A.

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