Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells

Yeast Rad52 DNA-repair mutants exhibit pronounced radiation sensitivity and a defect in homologous recombination (HR), whereas vertebrate cells lackin g Rad52 exhibit a nearly normal phenotype. Biochemical studies show that bo th yeast Rad52 and Rad55-57 (Rad51 paralogs) stimulate DNA-strand exchange mediated by Rad51. These findings raise the possibility that Rad51 paralogs may compensate for lack of Rad52 in vertebrate cells, explaining the absen ce of prominent phenotypes for Rad52-deficient cells. To test this hypothes is, using chicken DT40 cells, we generated conditional mutants deficient in both RAD52 and XRCC3, which is one of the five vertebrate PAD51 paralogs. Surprisingly, the rad52 xrcc3 double-mutant cells were non-viable and exhib ited extensive chromosomal breaks, whereas rad52 and xrcc3 single mutants g rew well. Our data reveal an overlapping (but non-reciprocal) role for Rad5 2 and XRCC3 in repairing DNA double-strand breaks. The present study shows that Rad52 can play an important role in HR repair by partially substitutin g for a Rad51 paralog.