| First Author | Chen D | Year | 2008 |
| Journal | J Biol Chem | Volume | 283 |
| Issue | 22 | Pages | 15381-9 |
| PubMed ID | 18348985 | Mgi Jnum | J:137584 |
| Mgi Id | MGI:3801257 | Doi | 10.1074/jbc.M710296200 |
| Citation | Chen D, et al. (2008) E2F1 regulates the base excision repair gene XRCC1 and promotes DNA repair. J Biol Chem 283(22):15381-9 |
| abstractText | 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. |
