The controlling role of ATM in homologous recombinational repair of DNA damage

Ciaran Morrison, Eiichiro Sonoda, Noriaki Takao, Akira Shinohara, Ken-ichi Yamamoto, Shunichi Takeda

Research output: Contribution to journalArticle

232 Citations (Scopus)

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 languageEnglish
Pages (from-to)463-471
Number of pages9
JournalEMBO Journal
Volume19
Issue number3
Publication statusPublished - Feb 1 2000
Externally publishedYes

Fingerprint

Recombinational DNA Repair
Automatic teller machines
DNA Damage
Homologous Recombination
Repair
DNA
Ataxia Telangiectasia
Radiation Tolerance
Cell Cycle Checkpoints
Chickens
Radiation
Cells
Aberrations
Chromosomal Instability
Inborn Genetic Diseases
Joining
Double-Stranded DNA Breaks
Medical Genetics
Chromosome Aberrations
Genes

Keywords

  • Ataxia telangiectasia
  • Double strand breaks
  • Non-homologous end-joining
  • Nuclear foci
  • Recombination

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Morrison, C., Sonoda, E., Takao, N., Shinohara, A., Yamamoto, K., & Takeda, S. (2000). The controlling role of ATM in homologous recombinational repair of DNA damage. EMBO Journal, 19(3), 463-471.

The controlling role of ATM in homologous recombinational repair of DNA damage. / Morrison, Ciaran; Sonoda, Eiichiro; Takao, Noriaki; Shinohara, Akira; Yamamoto, Ken-ichi; Takeda, Shunichi.

In: EMBO Journal, Vol. 19, No. 3, 01.02.2000, p. 463-471.

Research output: Contribution to journalArticle

Morrison, C, Sonoda, E, Takao, N, Shinohara, A, Yamamoto, K & Takeda, S 2000, 'The controlling role of ATM in homologous recombinational repair of DNA damage', EMBO Journal, vol. 19, no. 3, pp. 463-471.
Morrison C, Sonoda E, Takao N, Shinohara A, Yamamoto K, Takeda S. The controlling role of ATM in homologous recombinational repair of DNA damage. EMBO Journal. 2000 Feb 1;19(3):463-471.
Morrison, Ciaran ; Sonoda, Eiichiro ; Takao, Noriaki ; Shinohara, Akira ; Yamamoto, Ken-ichi ; Takeda, Shunichi. / The controlling role of ATM in homologous recombinational repair of DNA damage. In: EMBO Journal. 2000 ; Vol. 19, No. 3. pp. 463-471.
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