| | |  | | | | Record from Web of Science® | | | | | | |
| Dual roles of ATM in the cellular response to radiation and in cell growth control |
|
|
| Author(s): Xu Y, Baltimore D |
| Source: GENES & DEVELOPMENT Volume: 10 Issue: 19 Pages: 2401-2410 Published: OCT 1 1996 |
| Times Cited: 257 References: 43 |
| Abstract: The gene mutated in ataxia-telangiectasia (AT) patients, denoted ATM, encodes a putative protein or lipid kinase. To elucidate the functions of ATM, we disrupted the mouse ATM gene through homologous recombination in mice. Consistent with cellular defects of AT patients, the ATM(-/-) cells are hypersensitive to gamma-irradiation and defective in cell-cycle arrest following radiation, correlating with a defective up-regulation of p53. In addition, ATM(-/-) mouse thymocytes are more resistant to apoptosis induced by gamma-irradiation than normal thymocytes. ATM(-/-) fibroblasts are inefficient in G(1) to S-phase progression following serum stimulation and senesce after only a few passages in culture. They have an increased constitutive level of p21(CIP1/WAF1). The ATM protein is therefore critical both for cellular responses to ionizing radiation and for normal cell-cycle progression. ATM(+/-) fibroblasts and thymocytes showed intermediately defective responses to irradiation but no growth defect, suggesting that the increased cancer risk of AT heterozygotes could be attributable to poor checkpoint function. |
| Document Type: Article |
| Language: English |
Addresses:
1. MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA |
| Publisher: COLD SPRING HARBOR LAB PRESS, 1 BUNGTOWN RD, PLAINVIEW, NY 11724 |
| Subject Category: Cell Biology; Developmental Biology; Genetics & Heredity |
| IDS Number: VM254 |
| ISSN: 0890-9369 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |