title: Regulation of ionizing radiation-induced Rad52 nuclear foci formation by c-Abl-mediated phosphorylation.
abstract: The RAD52 epistasis group of proteins, including Rad51, Rad52, and Rad54, plays an important role in the homologous recombination repair of double strand breaks. A well characterized feature associated with the ability of these proteins to repair double strand breaks is inducible nuclear foci formation at the sites of damage. How the process is functionally regulated in response to DNA damage, however, remains elusive. We show here that c-Abl tyrosine kinase associates with and phosphorylates Rad52 on tyrosine 104. Importantly, the very same site of Rad52 is phosphorylated on exposure of cells to ionizing radiation (IR). The functional significance of c-Abl-dependent phosphorylation of Rad52 is underscored by our findings that cells that express the phosphorylation-resistant Rad52 mutant, in which tyrosine 104 is replaced by phenylalanine, exhibit compromised nuclear foci formation in response to IR. Furthermore, IR-induced Rad52 nuclear foci formation is markedly suppressed by the expression of dominant-negative c-Abl. Together our data support a mode of post-translational regulation of Rad52 mediated by the c-Abl tyrosine kinase.
authors.affiliation: Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitao
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Yuan
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects*; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D051721:Rad52 DNA Repair and Recombination Protein; D011839:Radiation, Ionizing; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D051721:Rad52 DNA Repair and Recombination Protein; C497196:Rad52 protein, mouse; D011994:Recombinant Proteins; D016315:Proto-Oncogene Proteins c-abl