title: PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1.
abstract: The WD40-repeat protein DDB2 is essential for efficient recognition and subsequent removal of ultraviolet (UV)-induced DNA lesions by nucleotide excision repair (NER). However, how DDB2 promotes NER in chromatin is poorly understood. Here, we identify poly(ADP-ribose) polymerase 1 (PARP1) as a novel DDB2-associated factor. We demonstrate that DDB2 facilitated poly(ADP-ribosyl)ation of UV-damaged chromatin through the activity of PARP1, resulting in the recruitment of the chromatin-remodeling enzyme ALC1. Depletion of ALC1 rendered cells sensitive to UV and impaired repair of UV-induced DNA lesions. Additionally, DDB2 itself was targeted by poly(ADP-ribosyl)ation, resulting in increased protein stability and a prolonged chromatin retention time. Our in vitro and in vivo data support a model in which poly(ADP-ribosyl)ation of DDB2 suppresses DDB2 ubiquitylation and outline a molecular mechanism for PARP1-mediated regulation of NER through DDB2 stabilization and recruitment of the chromatin remodeler ALC1.
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Alex
authors.initials: A
authors.lastname: Pines
authors.forename: Mischa G
authors.initials: MG
authors.lastname: Vrouwe
authors.forename: Jurgen A
authors.initials: JA
authors.lastname: Marteijn
authors.forename: Dimitris
authors.initials: D
authors.lastname: Typas
authors.forename: Martijn S
authors.initials: MS
authors.lastname: Luijsterburg
authors.forename: Medine
authors.initials: M
authors.lastname: Cansoy
authors.forename: Paul
authors.initials: P
authors.lastname: Hensbergen
authors.forename: André
authors.initials: A
authors.lastname: Deelder
authors.forename: Anton
authors.initials: A
authors.lastname: de Groot
authors.forename: Syota
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
authors.forename: Nicolas
authors.initials: N
authors.lastname: Thoma
authors.forename: Wim
authors.initials: W
authors.lastname: Vermeulen
authors.forename: Harry
authors.initials: H
authors.lastname: Vrieling
authors.forename: Leon
authors.initials: L
authors.lastname: Mullenders
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D054875:Ubiquitination; D014466:Ultraviolet Rays
chemical_list: C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D004265:DNA Helicases; C543585:CHD1L protein, human