PubMed Journals: J Biol Chem
Source: PMID: 10212258
⇦ ⇨ J Biol Chem. 1999 Apr 30;274(18):12748-52.
Radiation-induced assembly of Rad51 and
Rad52 recombination complex requires ATM
Chen G(1), Yuan SS, Liu W, Xu Y, Trujillo
K, Song B, Cong F, Goff SP, Wu Y, Arlinghaus
R, Baltimore D, Gasser PJ, Park MS, Sung
P, Lee EY.
(1) Department of Molecular Medicine/Institute
The University of Texas Health Science Center at San Antonio,
San Antonio, Texas 78245, USA.
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.
PMID: 10212258 [Indexed for MEDLINE]