TY - JOUR
T1 - Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl
AU - Chen, Gang
AU - Yuan, Shyng Shiou F.
AU - Liu, Wei
AU - Xu, Yang
AU - Trujillo, Kelly
AU - Song, Binwei
AU - Cong, Feng
AU - Goff, Stephen P.
AU - Wu, Yun
AU - Arlinghaus, Ralph
AU - Baltimore, David
AU - Gasser, Paul J.
AU - Park, Min S.
AU - Sung, Patrick
AU - Lee, Eva Y.H.P.
PY - 1999/4/30
Y1 - 1999/4/30
N2 - Cells from individuals with the recessive cancer-prone disorder ataxia telangiectasia (A-T) are hypersensitive to ionizing radiation (I-R). ATM (mutated in A-T) is a protein kinase whose activity is stimulated by I-R. c- Abl, a nonreceptor tyrosine kinase, interacts with ATM and is activated by ATM following I-R. Rad51 is a homologue of bacterial RecA protein required for DNA recombination and repair. Here we demonstrate that there is an I-R- induced Rad51 tyrosine phosphorylation, and this induction is dependent on both ATM and c-Abl. ATM, c-Abl, and Rad51 can be co-immunoprecipitated from cell extracts. Consistent with the physical interaction, c-Abl phosphorylates Rad51 in vitro and in vivo. In assays using purified components, phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. After I- R, an increase in association between Rad51 and Rad52 occurs in wild-type cells but not in cells with mutations that compromise ATM or c-Abl. Our data suggest signaling mediated through ATM, and c-Abl is required for the correct posttranslational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R.
AB - Cells from individuals with the recessive cancer-prone disorder ataxia telangiectasia (A-T) are hypersensitive to ionizing radiation (I-R). ATM (mutated in A-T) is a protein kinase whose activity is stimulated by I-R. c- Abl, a nonreceptor tyrosine kinase, interacts with ATM and is activated by ATM following I-R. Rad51 is a homologue of bacterial RecA protein required for DNA recombination and repair. Here we demonstrate that there is an I-R- induced Rad51 tyrosine phosphorylation, and this induction is dependent on both ATM and c-Abl. ATM, c-Abl, and Rad51 can be co-immunoprecipitated from cell extracts. Consistent with the physical interaction, c-Abl phosphorylates Rad51 in vitro and in vivo. In assays using purified components, phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. After I- R, an increase in association between Rad51 and Rad52 occurs in wild-type cells but not in cells with mutations that compromise ATM or c-Abl. Our data suggest signaling mediated through ATM, and c-Abl is required for the correct posttranslational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R.
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U2 - 10.1074/jbc.274.18.12748
DO - 10.1074/jbc.274.18.12748
M3 - Article
C2 - 10212258
AN - SCOPUS:0033617368
SN - 0021-9258
VL - 274
SP - 12748
EP - 12752
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 18
ER -