| First Author | Yamamoto K | Year | 2012 |
| Journal | J Cell Biol | Volume | 198 |
| Issue | 3 | Pages | 305-13 |
| PubMed ID | 22869596 | Mgi Jnum | J:191288 |
| Mgi Id | MGI:5461411 | Doi | 10.1083/jcb.201204098 |
| Citation | Yamamoto K, et al. (2012) Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice. J Cell Biol 198(3):305-13 |
| abstractText | Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic acid (DNA) damage responses by phosphorylating numerous substrates implicated in DNA repair and cell cycle checkpoint activation. A-T patients and mouse models that express no ATM protein undergo normal embryonic development but exhibit pleiotropic DNA repair defects. In this paper, we report that mice carrying homozygous kinase-dead mutations in Atm (Atm(KD/KD)) died during early embryonic development. Atm(KD/-) cells exhibited proliferation defects and genomic instability, especially chromatid breaks, at levels higher than Atm(-/-) cells. Despite this increased genomic instability, Atm(KD/-) lymphocytes progressed through variable, diversity, and joining recombination and immunoglobulin class switch recombination, two events requiring nonhomologous end joining, at levels comparable to Atm(-/-) lymphocytes. Together, these results reveal an essential function of ATM during embryogenesis and an important function of catalytically inactive ATM protein in DNA repair. |
