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

Mei Ming; Christopher R. Shea; Xiumei Guo; Xiaoling Li; Keyoumars Soltani; Weinong Han; Yu Ying He

doi:10.1073/pnas.1010377108

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

Mei Ming, Christopher R. Shea, Xiumei Guo, Xiaoling Li, Keyoumars Soltani, Weinong Han, Yu Ying He

Johns Hopkins Hospital

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

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,weshowthat SIRT1 levels are significantly reduced inhuman skin tumors from Caucasian patients, a population at highest risk. Thesefindings suggest that SIRT1 acts as a tumor suppressor through its role in DNA repair.

Original language	English (US)
Pages (from-to)	22623-22628
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	107
Issue number	52
DOIs	https://doi.org/10.1073/pnas.1010377108
State	Published - Dec 28 2010

Keywords

AKT
PTEN
UVB

ASJC Scopus subject areas

General

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10.1073/pnas.1010377108

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Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C. / Ming, Mei; Shea, Christopher R.; Guo, Xiumei; Li, Xiaoling; Soltani, Keyoumars; Han, Weinong; He, Yu Ying.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 52, 28.12.2010, p. 22623-22628.

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

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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,weshowthat SIRT1 levels are significantly reduced inhuman skin tumors from Caucasian patients, a population at highest risk. Thesefindings suggest that SIRT1 acts as a tumor suppressor through its role in DNA repair.",

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