GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:21149730

From GONUTS
Jump to: navigation, search
Citation

Ming, M, Shea, CR, Guo, X, Li, X, Soltani, K, Han, W and He, YY (2010) Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C. Proc. Natl. Acad. Sci. U.S.A. 107:22623-8

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.

Links

PubMed PMC3012476 Online version:10.1073/pnas.1010377108

Keywords

Animals; Base Sequence; Blotting, Western; Cell Nucleus/metabolism; Cells, Cultured; DNA Damage; DNA Repair/genetics; DNA Repair/physiology; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Embryo, Mammalian/cytology; European Continental Ancestry Group; Fibroblasts/cytology; Fibroblasts/metabolism; Fibroblasts/radiation effects; Genome/genetics; Humans; Immunohistochemistry; Keratinocytes/cytology; Keratinocytes/metabolism; Keratinocytes/radiation effects; Mice; Mice, Knockout; Proto-Oncogene Proteins c-akt/metabolism; RNA Interference; Reverse Transcriptase Polymerase Chain Reaction; Sirtuin 1/genetics; Sirtuin 1/metabolism; Skin Neoplasms/genetics; Skin Neoplasms/metabolism; Skin Neoplasms/pathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SIRT1

involved_in

GO:0051898: negative regulation of protein kinase B signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SIRT1

involved_in

GO:0000720: pyrimidine dimer repair by nucleotide-excision repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SIRT1

involved_in

GO:0051898: negative regulation of protein kinase B signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SIRT1

involved_in

GO:0000720: pyrimidine dimer repair by nucleotide-excision repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SIR1

involved_in

GO:0051898: negative regulation of protein kinase B signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SIR1

involved_in

GO:0000720: pyrimidine dimer repair by nucleotide-excision repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SIR1

involved_in

GO:0000720: pyrimidine dimer repair by nucleotide-excision repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SIR1

involved_in

GO:0051898: negative regulation of protein kinase B signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.