Faculty Collaboration Database

Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. J Biol Chem 1999 Apr 30;274(18):12748-52

Date

04/23/1999

Pubmed ID

10212258

DOI

10.1074/jbc.274.18.12748

Scopus ID

2-s2.0-0033617368 (requires institutional sign-in at Scopus site)   246 Citations

Abstract

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.

Author List

Chen G, 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

Author

Paul Gasser BS,MS,PhD Assistant Professor in the Biomedical Sciences department at Marquette University

MESH terms used to index this publication - Major topics in bold

Ataxia Telangiectasia Mutated Proteins
Cell Cycle Proteins
Checkpoint Kinase 2
DNA-Binding Proteins
Phosphorylation
Protein Binding
Protein Kinases
Protein Processing, Post-Translational
Proteins
Proto-Oncogene Proteins c-abl
Rad51 Recombinase
Rad52 DNA Repair and Recombination Protein
Recombination, Genetic
Saccharomyces cerevisiae Proteins
Tumor Suppressor Proteins
Tyrosine