Abstract
The human genetic disorder ataxia telangiectasia (A-T), caused by mutation in the ATM gene, is characterized by chromosomal instability, radiosensitivity and defective cell cycle checkpoint activation. DNA double-strand breaks (dsbs) persist in A-T cells after irradiation, but the underlying defect is unclear. To investigate ATM's interactions with dsb repair pathways, we disrupted ATM along with other genes involved in the principal, complementary dsb repair pathways of homologous recombination (HR) or non-homologous end-joining (NHEJ) in chicken DT40 cells. ATM(-/-) cells show altered kinetics of radiation-induced Rad51 and Rad54 focus formation. Ku70-deficient (NHEJ-) ATM(-/-) chicken DT40 cells show radiosensitivity and high radiation-induced chromosomal aberration frequencies, while Rad54-defective (HR-) ATM(-/-) cells show only slightly elevated aberration levels after irradiation, placing ATM and HR on the same pathway. These results reveal that ATM defects impair HR-mediated dsb repair and may link cell cycle checkpoints to HR activation.
| Original language | English |
|---|---|
| Pages (from-to) | 463-471 |
| Number of pages | 9 |
| Journal | EMBO Journal |
| Volume | 19 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Feb 1 2000 |
| Externally published | Yes |
Keywords
- Ataxia telangiectasia
- Double strand breaks
- Non-homologous end-joining
- Nuclear foci
- Recombination
ASJC Scopus subject areas
- Neuroscience(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)