c-Abl tyrosine kinase is not essential for ataxia telangiectasia mutated functions in chromosomal maintenance

Noriaki Takao, Ryoichi Mori, Hideaki Kato, Akira Shinohara, Ken Ichi Yamamoto

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

c-Abl is activated by DNA damage in an ataxia telangiectasia mutated (ATM)-dependent manner and plays important roles in growth arrest and apoptosis induced by DNA damage. c-Abl also interacts physically and functionally with Rad51, a key molecule in homologous recombinational (HR) DNA repair. To study further the roles of c-Abl in HR DNA repair, we generated c-Abl(-/-) and ATM(-/-)/c-Abl(-/-) mutant cell lines from a chicken B lymphocyte DT40 cell line, comparing the phenotypes of these mutants to those of ATM(-/-) DT40 cells that we had created previously. We found that the time course of radiation-induced Rad51 focus formation is abnormal in ATM(-/-) DT40 cells, consistent with the observation that ATM(-/-) DT40 cells display hypersensitivity to ionizing radiation and highly elevated frequencies of both spontaneous and radiation-induced chromosomal aberrations. In contrast, c-Abl(-/-) cells did not show these ATM-related defects in their cellular response to radiation, nor did the disruption of c- Abl in ATM(-/-) DT40 cells exacerbate these ATM-related defects. However, c- Abl(-/-) DT40 cells, but not ATM(-/-) DT40 cells, were resistant to radiation-induced apoptosis, indicating an important role for c-Abl in this cellular response to ionizing radiation. These results therefore indicate that, although ATM plays an important role in genome maintenance, c-Abl is not essential for this ATM function. These findings suggest that c-Abl and ATM play important roles in the maintenance of the cell homeostasis in response to DNA damage that are, at least in part, independent.

Original languageEnglish
Pages (from-to)725-728
Number of pages4
JournalJournal of Biological Chemistry
Volume275
Issue number2
DOIs
Publication statusPublished - Jan 14 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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