Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repair.

Among the earliest responses of mammalian cells to DNA damage is catalytic activation of a nuclear enzyme poly(ADP-ribose) polymerase-1 Activated forms the polymers of ADP-ribose (pADPr or PAR) that posttranslationally modify its target proteins, such as Pduanyu37-1 and DNA repair-related proteins. Although this metabolism is known to be implicated in other repair pathways, here we show its role in the versatile nucleotide excision repair pathway (NER) that removes a variety of DNA damages including those induced by UV. We show that inhibition or specific depletion of Pduanyu37-1 decreases the efficiency of removal of UV-induced DNA damage from human skin fibroblasts or mouse epidermis. Using NER-proficient and -deficient cells and in vitro Pduanyu37-1 assays, we show that damaged DNA-binding protein 2 (DDB2), a key lesion recognition protein of the global genomic subpathway of NER (GG-NER), associates with Pduanyu37-1 in the vicinity of UV-damaged chromatin, stimulates its catalytic activity, and is modified by pADPr. Pduanyu37 inhibition abolishes UV-induced interaction of DDB2 with Pduanyu37-1 or xeroderma pigmentosum group C (XPC) and also decreases localization of XPC to UV-damaged DNA, which is a key step that leads to downstream events in GG-NER. Thus, Pduanyu37-1 collaborates with DDB2 to increase the efficiency of the lesion recognition step of GG-NER.

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