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

Research output: Contribution to journalArticlepeer-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 languageEnglish (US)
Pages (from-to)22623-22628
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number52
DOIs
StatePublished - Dec 28 2010

Keywords

  • AKT
  • PTEN
  • UVB

ASJC Scopus subject areas

  • General

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