Ionizing radiation-induced foci formation of mammalian Rad51 and Rad54 depends on the Rad51 paralogs, but not on Rad52.
Homologous recombination is of major importance for the prevention of genomic instability during chromosome duplication and repair of DNA damage, especially double-strand breaks. Biochemical experiments have revealed that during the process of homologous recombination the RAD52 group proteins, including Rad51, Rad52 and Rad54, are involved in an essential step: formation of a joint molecule between the broken DNA and the intact repair template. Accessory proteins for this reaction include the Rad51 paralogs and BRCA2. The significance of homologous recombination for the cell is underscored by the evolutionary conservation of the Rad51, Rad52 and Rad54 proteins from yeast to humans. Upon treatment of cells with ionizing radiation, the RAD52 group proteins accumulate at the sites of DNA damage into so-called foci. For the yeast Saccharomyces cerevisiae, foci formation of Rad51 and Rad54 is abrogated in the absence of Rad52, while Rad51 foci formation does occur in the absence of the Rad51 paralog Rad55. By contrast, we show here that in mammalian cells, Rad52 is not required for foci formation of Rad51 and Rad54. Furthermore, radiation-induced foci formation of Rad51 and Rad54 is impaired in all Rad51 paralog and BRCA2 mutant cell lines tested, while Rad52 foci formation is not influenced by a mutation in any of these recombination proteins. Despite their evolutionary conservation and biochemical similarities, S. cerevisiae and mammalian Rad52 appear to differentially contribute to the DNA-damage response.
van Veelen
Lieneke R
LR
Department of Cell Biology and Genetics, Erasmus MC, University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Essers
Jeroen
J
van de Rakt
Mandy W M M
MW
Odijk
Hanny
H
Pastink
Albert
A
Zdzienicka
Małgorzata Z
MZ
Paulusma
Coen C
CC
Kanaar
Roland
R
D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D006224:Cricetinae; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000032:analysis*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis*; D051135:Rad51 Recombinase; D051721:Rad52 DNA Repair and Recombination Protein; D011839:Radiation, Ionizing; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; C497196:Rad52 protein, mouse; D029701:Saccharomyces cerevisiae Proteins; C495151:RAD51 protein, S cerevisiae; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse; D004265:DNA Helicases; C103532:RAD54L protein, human