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PMID: 16030353 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

DNA repair factor XPC is modified by SUMO-1 and ubiquitin following UV irradiation.

Nucleic acids research ·Vol. 33 ·No. 13 ·2005-00-00 ·Pages 4023-34

Wang QE, Zhu Q, Wani G, El-Mahdy MA, Li J, Wani AA

Abstract

Nucleotide excision repair (NER) is the major DNA repair process that removes diverse DNA lesions including UV-induced photoproducts. There are more than 20 proteins involved in NER. Among them, XPC is thought to be one of the first proteins to recognize DNA damage during global genomic repair (GGR), a sub-pathway of NER. In order to study the mechanism through which XPC participates in GGR, we investigated the possible modifications of XPC protein upon UV irradiation in mammalian cells. Western blot analysis of cell lysates from UV-irradiated normal human fibroblast, prepared by direct boiling in an SDS lysis buffer, showed several anti-XPC antibody-reactive bands with molecular weight higher than the original XPC protein. The reciprocal immunoprecipitation and siRNA transfection analysis demonstrated that XPC protein is modified by SUMO-1 and ubiquitin. By using several NER-deficient cell lines, we found that DDB2 and XPA are required for UV-induced XPC modifications. Interestingly, both the inactivation of ubiquitylation and the treatment of proteasome inhibitors quantitatively inhibited the UV-induced XPC modifications. Furthermore, XPC protein is degraded significantly following UV irradiation in XP-A cells in which sumoylation of XPC does not occur. Taken together, we conclude that XPC protein is modified by SUMO-1 and ubiquitin following UV irradiation and these modifications require the functions of DDB2 and XPA, as well as the ubiquitin-proteasome system. Our results also suggest that at least one function of UV-induced XPC sumoylation is related to the stabilization of XPC protein.

MeSH Terms
Cell Line DNA-Binding Proteins/metabolism,physiology Fibroblasts/metabolism,radiation effects Humans Proteasome Endopeptidase Complex/metabolism SUMO-1 Protein/metabolism Ubiquitin/metabolism Ultraviolet Rays Xeroderma Pigmentosum Group A Protein
Chemicals
DDB2 protein, human DNA-Binding Proteins SUMO-1 Protein Ubiquitin XPA protein, human Xeroderma Pigmentosum Group A Protein XPC protein, human Proteasome Endopeptidase Complex
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wang Qi-En
Department of Radiology, The Ohio State University 103 Wiseman Hall, 400 W. 12th Avenue, Columbus, OH 43210, USA.
Zhu Qianzheng
Wani Gulzar
El-Mahdy Mohamed A
Li Jinyou
Wani Altaf A
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gki684
Published
2005-00-00
Epub
2005-00-19
Pages
4023-34
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1178000
Subset
IM
Grants
NIEHS NIH HHS · ES6074 · United States
NIEHS NIH HHS · R01 ES012991 · United States
NCI NIH HHS · R01 CA093413 · United States
NIEHS NIH HHS · ES12991 · United States
NCI NIH HHS · CA93413 · United States
Corrections
ErratumIn
PMID: 34850104
External Links
PubMed source DOI: 10.1093/nar/gki684 PMC Full Text View journal details
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