| First Author | Ouyang Y | Year | 2006 |
| Journal | Mutat Res | Volume | 596 |
| Issue | 1-2 | Pages | 64-75 |
| PubMed ID | 16488448 | Mgi Jnum | J:107713 |
| Mgi Id | MGI:3621700 | Doi | 10.1016/j.mrfmmm.2005.12.016 |
| Citation | Ouyang Y, et al. (2006) Loss of Ubr2, an E3 ubiquitin ligase, leads to chromosome fragility and impaired homologous recombinational repair. Mutat Res 596(1-2):64-75 |
| abstractText | The N-end rule pathway of protein degradation targets proteins with destabilizing N-terminal residues. Ubr2 is one of the E3 ubiquitin ligases of the mouse N-end rule pathway. We have previously shown that Ubr2(-/-) male mice are infertile, owing to the arrest of spermatocytes between the leptotene/zygotene and pachytene of meiosis I, the failure of chromosome pairing, and subsequent apoptosis. Here, we report that mouse fibroblast cells derived from Ubr2(-/-) embryos display genome instability. The frequency of chromosomal bridges and micronuclei were much higher in Ubr2(-/-) fibroblasts than in +/+ controls. Metaphase chromosome spreads from Ubr2(-/-) cells revealed a high incidence of spontaneous chromosomal gaps, indicating chromosomal fragility. These fragile sites were generally replicated late in S phase. Ubr2(-/-) cells were hypersensitive to mitomycin C, a DNA cross-linking agent, but displayed normal sensitivity to gamma-irradiation. A reporter assay showed that Ubr2(-/-) cells are significantly impaired in the homologous recombination repair of a double strand break. In contrast, Ubr2(-/-) cells appeared normal in an assay for non-homologous end joining. Our results therefore unveil the role of the ubiquitin ligase Ubr2 in maintaining genome integrity and in homologous recombination repair. |
