Localization and dynamic relocalization of mammalian Rad52 during the cell cycle and in response to DNA damage

The importance of RAD52 in establishment and maintenance of genomic structure has been established by genetic experiments in the yeast Saccharomyces cerevisiae, where mutation of RAD52 has been shown to diminish DNA repair and recombination of a variety of markers, including the rDNA [1-3]. Biochemical analysis has shown that yeast and mammalian Rad52 proteins have some identical functions in vitro [4-6], but targeted deletion of Rad52 in vertebrates has little effect on repair and recombination [7,8]. These results raise the question of whether mammalian Rad52 does indeed function in recombination and/or repair. Here we show that Rad52 is distributed throughout the nucleoplasm in actively cycling mammalian cells and is localized specifically to the nucleoli in S phase. In response to ionizing radiation, Rad52 relocalizes to form distinctive foci which are distributed throughout the nucleus and which colocalize with Rad50 foci in the DNA damage response. These data suggest that rDNA recombination and DNA repair are functions shared by mammalian Rad52 and its S. cerevisiae homolog, and provide evidence for the coordinated action of Rad50 and Rad52 in DNA repair.