Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl

Gang Chen, Shyng Shiou F. Yuan, Wei Liu, Yang Xu, Kelly Trujillo, Binwei Song, Feng Cong, Stephen P. Goff, Yun Wu, Ralph Arlinghaus, David Baltimore, Paul J. Gasser, Min S. Park, Patrick Sung, Eva Y.H.P. Lee

Research output: Contribution to journalArticle

227 Scopus 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 posttranslational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R.

Original languageEnglish (US)
Pages (from-to)12748-12752
Number of pages5
JournalJournal of Biological Chemistry
Volume274
Issue number18
DOIs
StatePublished - Apr 30 1999

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chen, G., Yuan, S. S. F., Liu, W., Xu, Y., Trujillo, K., Song, B., Cong, F., Goff, S. P., Wu, Y., Arlinghaus, R., Baltimore, D., Gasser, P. J., Park, M. S., Sung, P., & Lee, E. Y. H. P. (1999). Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. Journal of Biological Chemistry, 274(18), 12748-12752. https://doi.org/10.1074/jbc.274.18.12748