Role of oxidation of XRCC1 protein in regulation of mammalian DNA repair process

Abstract

Influence of XRCC1 protein oxidation on the modification of proteins catalyzed by poly(ADP‑ribose)polyme-rases (PARP1 and PARP2) has been studied for the first time. XRCC1, PARP1 and PARP2 are responsible for coordination of multistep repair of most abundant DNA lesions, functioning as scaffold proteins. We have shown that the XRCC1 oxidation reduces the efficiency of its ADP‑ribosylation and the protein affinity for poly(ADP‑ribose). The ADP‑ribose modification of various XRCC1 forms is enhanced in the presence of DNA polymerase b (Polb) capable to form a stable complex with XRCC1. The oxidation suppresses the inhibiting activity of XRCC1 and its complex with Polb towards the automodification of PARP1 and PARP2 that may enhance the efficiency of repair. The results of this study indicate that the oxidation of XRCC1 play a role in fine regulation of poly(ADP‑ribosyl)ation levels of proteins and their coordinating functions in the DNA repair.