| First Author | Deans B | Year | 2000 |
| Journal | EMBO J | Volume | 19 |
| Issue | 24 | Pages | 6675-85 |
| PubMed ID | 11118202 | Mgi Jnum | J:66529 |
| Mgi Id | MGI:1928590 | Doi | 10.1093/emboj/19.24.6675 |
| Citation | Deans B, et al. (2000) Xrcc2 is required for genetic stability, embryonic neurogenesis and viability in mice. EMBO J 19(24):6675-85 |
| abstractText | Repair of DNA damage by homologous recombination has only recently been established as an important mechanism in maintaining genetic stability in mammalian cells. The recently cloned Xrcc2 gene is a member of the mammalian Rad51 gene family, thought to be central to homologous recombination repair. To understand its function in mammals, we have disrupted Xrcc2 in mice. No Xrcc2(-/-) animals were found alive, with embryonic lethality occurring from mid-gestation. Xrcc2(-/-) embryos surviving until later stages of embryogenesis commonly showed developmental abnormalities and died at birth. Neonatal lethality, apparently due to respiratory failure, was associated with a high frequency of apoptotic death of post- mitotic neurons in the developing brain, leading to abnormal cortical structure. Embryonic cells showed genetic instability, revealed by a high level of chromosomal aberrations, and were sensitive to gamma-rays. Our findings demonstrate that homologous recombination has an important role in endogenous damage repair in the developing embryo. Xrcc2 disruption identifies a range of defects that arise from malfunction of this repair pathway, and establishes a previously unidentified role for homologous recombination repair in correct neuronal development. |
