Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl.
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 post-translational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R.
Chen
G
G
Department of Molecular Medicine/Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245, USA.
Yuan
S S
SS
Liu
W
W
Xu
Y
Y
Trujillo
K
K
Song
B
B
Cong
F
F
Goff
S P
SP
Wu
Y
Y
Arlinghaus
R
R
Baltimore
D
D
Gasser
P J
PJ
Park
M S
MS
Sung
P
P
Lee
E Y
EY
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D004268:DNA-Binding Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D051135:Rad51 Recombinase; D051721:Rad52 DNA Repair and Recombination Protein; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D014443:Tyrosine / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D014443:Tyrosine; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; D016315:Proto-Oncogene Proteins c-abl; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D051135:Rad51 Recombinase