title: Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repair.
abstract: Among the earliest responses of mammalian cells to DNA damage is catalytic activation of a nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1). Activated PARP-1 forms the polymers of ADP-ribose (pADPr or PAR) that posttranslationally modify its target proteins, such as PARP-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 PARP inhibition or specific depletion of PARP-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 PARP-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 PARP-1 in the vicinity of UV-damaged chromatin, stimulates its catalytic activity, and is modified by pADPr. PARP inhibition abolishes UV-induced interaction of DDB2 with PARP-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, PARP-1 collaborates with DDB2 to increase the efficiency of the lesion recognition step of GG-NER.
authors: Laboratory for Skin Cancer Research, Hospital Research Centre of  Laval University (CHUL) and Centre Hospitalier Universitaire du Quebec (CHUQ), Laval University, Quebec, QC,  Canada G1V 4G2.
authors: Mihaela
authors: M
authors: Robu
authors: Rashmi G
authors: RG
authors: Shah
authors: Nancy
authors: N
authors: Petitclerc
authors: Julie
authors: J
authors: Brind'Amour
authors: Febitha
authors: F
authors: Kandan-Kulangara
authors: Girish M
authors: GM
authors: Shah
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008812:Mice, Hairless; D010616:Phenanthrenes / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D034622:RNA Interference; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C086984:XPC protein, human; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases