TY - JOUR
T1 - The absence of a functional relationship between ATM and BLM, the components of BASC, in DT40 cells
AU - Wang, Wensheng
AU - Seki, Masayuki
AU - Otsuki, Makoto
AU - Tada, Shusuke
AU - Takao, Noriaki
AU - Yamamoto, Ken Ichi
AU - Hayashi, Makoto
AU - Honma, Masamitsu
AU - Enomoto, Takemi
N1 - Funding Information:
We thank Dr. Takeda for kindly providing the RAD54 -Hygromycin® vector. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Science, Sports, and Technology of Japan, a Health Sciences Research Grant from the Ministry of Health, Labor, and Welfare of Japan, and a grant from the Uehara Memorial Foundation. M. Seki was supported in part by the Mochida Memorial Foundation for Medical and Pharmaceutical Research.
PY - 2004/3/2
Y1 - 2004/3/2
N2 - 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.
AB - 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.
KW - ATM
KW - BASC
KW - BLM
KW - DSB
KW - SCE
KW - Targeted integration
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U2 - 10.1016/j.bbadis.2003.11.008
DO - 10.1016/j.bbadis.2003.11.008
M3 - Article
C2 - 14990344
AN - SCOPUS:1342306874
SN - 0925-4439
VL - 1688
SP - 137
EP - 144
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 2
ER -