HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 22, 15381-15389, May 30, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/22/15381    most recent M710296200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, D. Articles by Lopez, C. D. Search for Related Content PubMed PubMed Citation Articles by Chen, D. Articles by Lopez, C. D. Social Bookmarking                      What's this?

E2F1 Regulates the Base Excision Repair Gene XRCC1 and Promotes DNA Repair^*

From the Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, Oregon 97239

The E2F1 transcription factor activates S-phase-promoting genes, mediates apoptosis, and stimulates DNA repair through incompletely understood mechanisms. XRCC1 (x-ray repair cross-complementing group 1) protein is important for efficient single strand break/base excision repair. Although both damage and proliferative signals increase XRCC1 levels, the mechanisms regulating XRCC1 transcription remain unclear. To study these upstream mechanisms, the XRCC1 promoter was cloned into a luciferase reporter. Ectopic expression of wild-type E2F1, but not an inactive mutant E2F1(132E), activated the XRCC1 promoter-luciferase reporter, and deletion of predicted E2F1 binding sites in the promoter attenuated E2F1-induced activation. Endogenous XRCC1 expression increased in cells conditionally expressing wild-type, but not mutant E2F1, and methyl methanesulfonate-induced DNA damage stimulated XRCC1 expression in E2F1^+/+ but not E2F1^-/- mouse embryo fibroblasts (MEFs). Additionally, E2F1^-/- MEFs displayed attenuated DNA repair after methyl methanesulfonate-induced damage compared with E2F1^+/+ MEFs. Moreover, Chinese hamster ovary cells with mutant XRCC1 (EM9) were more sensitive to E2F1-induced apoptosis compared with Chinese hamster ovary cells with wild-type XRCC1 (AA8). These results provide new mechanistic insight into the role of the E2F pathway in maintaining genomic stability.

Received for publication, December 18, 2008 , and in revised form, March 12, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health, Grant CA104997 (to C. D. L.). This work was also supported by the Oregon Health and Science University Division of Hematology and Medical Oncology and the Oregon Health and Science University Cancer Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Present address: Dept. of Medicine, Beijing You An Hospital, Capital University of Medical Sciences, Beijing 100054, China.

² Present address: Dept. of Surgery, Shandong Tumor Hospital, Jinan Shandong 250117, China.

³ To whom correspondence should be addressed: Dept. of Medicine, Division of Hematology and Medical Oncology, Mail Code: L586B, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97239. Tel.: 503-494-8321; Fax: 503-418-0844; E-mail: lopezc{at}ohsu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Huang, L. Li, and L. Yu XRCC1 Arg399Gln, Arg194Trp and Arg280His polymorphisms in breast cancer risk: a meta-analysis Mutagenesis, July 1, 2009; 24(4): 331 - 339. [Abstract] [Full Text] [PDF]

				S. Wang, Z. Gong, R. Chen, Y. Liu, A. Li, G. Li, and J. Zhou JWA regulates XRCC1 and functions as a novel base excision repair protein in oxidative-stress-induced DNA single-strand breaks Nucleic Acids Res., April 1, 2009; 37(6): 1936 - 1950. [Abstract] [Full Text] [PDF]