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.
|Number of pages||8|
|Journal||Biochimica et Biophysica Acta - Molecular Basis of Disease|
|Publication status||Published - Mar 2 2004|
- Targeted integration
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology