Simultaneous depletion of WRNIP1 and RAD52 restores resistance to oxidative stress

Abstract

WRNIP1 was originally identified as Werner (WRN) helicase interacting protein in a yeast two-hybrid screen. The WRN helicase, which is mutated in the progeroid disorder Werner syndrome , has been implicated in homologous recombination, DNA repair, and other DNA transactions. WRN also interacts with RAD52, which is conserved from yeast to human and may function in homolo-gous recombination under certain conditions. In this study, we addressed the physical and functional relationship between WRNIP1 and RAD52. WRNIP1 and RAD52 formed a complex in cells. WRNIP1 and RAD52 double gene knockout cells grew slightly slower than each of the single gene knockout cell lines and wild-type cells, indicating that WRNIP1 and RAD52 are required to maintain the normal rate of cell growth. Interestingly, the sensitivity to hydrogen peroxide of each single gene knockout cell line was suppressed in double gene knockout cells, suggesting that a new pathway dealing with oxidative stress-induced DNA lesions operates in the absence of both WRNIP1 and RAD52.