title: 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.
authors.affiliation: Section of Dermatology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Ming
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Shea
authors.forename: Xiumei
authors.initials: X
authors.lastname: Guo
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Keyoumars
authors.initials: K
authors.lastname: Soltani
authors.forename: Weinong
authors.initials: W
authors.lastname: Han
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: He
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016678:Genome / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D044465:White People
chemical_list: D004268:DNA-Binding Proteins; C086984:XPC protein, human; D051057:Proto-Oncogene Proteins c-akt; C447939:SIRT1 protein, human; D056564:Sirtuin 1