The absence of a functional relationship between ATM and BLM, the components of BASC, in DT40 cells

Wensheng Wang, Masayuki Seki, Makoto Otsuki, Shusuke Tada, Noriaki Takao, Ken Ichi Yamamoto, Makoto Hayashi, Masamitsu Honma, Takemi Enomoto

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6 Citations (Scopus)

Abstract

Bloom syndrome (BS) and ataxia-telangiectasia (A-T) are rare autosomal recessive diseases associated with chromosomal instability. The genes responsible for BS and A-T have been identified as BLM and ATM, respectively, whose products were recently found to be components of BRCA1-associated genome surveillance complex (BASC), a supercomplex possibly involved in the recognition and repair of aberrant DNA structures. Based on experiments using BLM-/- DT40 cells and BLM-/-/RAD54-/- DT40 cells, we previously suggested that BLM functions to reduce the formation of double-strand breaks (DSBs) during DNA replication. To examine whether ATM is involved in the recognition and/or repair of DSBs generated in BLM -/- DT40 cells and to address the functional relationship between the two BASC components, we generated BLM-/-/ATM-/- DT40 cells and characterized their properties as well as those of ATM-/- and BLM-/- DT40 cells. BLM-/-/ATM-/- cells proliferated slightly more slowly than either BLM-/- or ATM -/- cells. The sensitivity of BLM-/-/ATM-/- cells to γ-irradiation was similar to that of ATM-/- cells, while BLM-/- cells were slightly resistant to γ-irradiation compared with wild-type cells. BLM-/- cells showed sensitivity to methyl methanesulfonate (MMS) and UV irradiation while ATM-/- cells did not show sensitivity to either agent. The sensitivity of BLM -/-/ATM-/- cells to MMS and UV was similar to that of BLM-/- cells. Disrupting the function of ATM reduced the targeted integration frequency in BLM-/- DT40 cells. However, a defect in ATM only slightly reduced the increased sister chromatid exchanges (SCEs) in BLM-/- DT40 cells.

Original languageEnglish
Pages (from-to)137-144
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1688
Issue number2
DOIs
Publication statusPublished - Mar 2 2004

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Keywords

  • ATM
  • BASC
  • BLM
  • DSB
  • SCE
  • Targeted integration

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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