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

Biochim Biophys Acta. 2004 Mar 2;1688(2):137-44. doi: 10.1016/j.bbadis.2003.11.008.

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 gamma-irradiation was similar to that of ATM(-/-) cells, while BLM(-/-) cells were slightly resistant to gamma-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / deficiency
  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / physiology
  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • BRCA1 Protein / physiology
  • Cell Count
  • Cell Cycle Proteins
  • Cell Line / pathology
  • Cell Line / radiation effects
  • Cell Survival
  • Chickens
  • DNA Damage*
  • DNA Helicases / deficiency
  • DNA Helicases / genetics*
  • DNA Helicases / physiology
  • DNA-Binding Proteins
  • Gamma Rays
  • Genetic Vectors
  • Methyl Methanesulfonate
  • Protein Serine-Threonine Kinases / deficiency
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / physiology
  • RecQ Helicases
  • Sister Chromatid Exchange
  • Transfection
  • Tumor Suppressor Proteins
  • Ultraviolet Rays

Substances

  • BRCA1 Protein
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • Methyl Methanesulfonate
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases
  • Adenosine Triphosphatases
  • Bloom syndrome protein
  • DNA Helicases
  • RecQ Helicases