title: SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair.
abstract: XPC recognizes UV-induced DNA lesions and initiates their removal by nucleotide excision repair (NER). Damage recognition in NER is tightly controlled by ubiquitin and SUMO modifications. Recent studies have shown that the SUMO-targeted ubiquitin ligase RNF111 promotes K63-linked ubiquitylation of SUMOylated XPC after DNA damage. However, the exact regulatory function of these modifications in vivo remains elusive. Here we show that RNF111 is required for efficient repair of ultraviolet-induced DNA lesions. RNF111-mediated ubiquitylation promotes the release of XPC from damaged DNA after NER initiation, and is needed for stable incorporation of the NER endonucleases XPG and ERCC1/XPF. Our data suggest that RNF111, together with the CRL4(DDB2) ubiquitin ligase complex, is responsible for sequential XPC ubiquitylation, which regulates the recruitment and release of XPC and is crucial for efficient progression of the NER reaction, thereby providing an extra layer of quality control of NER.
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands Erasmus MC, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
authors.forename: Loes
authors.initials: L
authors.lastname: van Cuijk
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Dr Molewaterplein 50, Rotterdam 3015 GE, The Netherlands.
authors.forename: Gijsbert J
authors.initials: GJ
authors.lastname: van Belle
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands Erasmus MC, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Turkyilmaz
authors.affiliation: Ubiquitin Signaling Group, Protein Signaling Program, The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3B, Copenhagen DK-2200, Denmark.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Poulsen
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands Erasmus MC, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
authors.forename: Roel C
authors.initials: RC
authors.lastname: Janssens
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands Erasmus MC, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
authors.forename: Arjan F
authors.initials: AF
authors.lastname: Theil
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands Erasmus MC, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Sabatella
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands Erasmus MC, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
authors.forename: Hannes
authors.identifier: 0000000344175358
authors.initials: H
authors.lastname: Lans
authors.affiliation: Ubiquitin Signaling Group, Protein Signaling Program, The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3B, Copenhagen DK-2200, Denmark.
authors.forename: Niels
authors.identifier: 000000026623709X
authors.initials: N
authors.lastname: Mailand
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Dr Molewaterplein 50, Rotterdam 3015 GE, The Netherlands.
authors.forename: Adriaan B
authors.initials: AB
authors.lastname: Houtsmuller
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands Erasmus MC, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Vermeulen
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands Erasmus MC, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
authors.forename: Jurgen A
authors.initials: JA
authors.lastname: Marteijn
mesh_terms: D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D025842:SUMO-1 Protein; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D000099250:DNA Excision Repair Protein ERCC-5; C086984:XPC protein, human; C486067:RNF111 protein, human; C071447:ERCC1 protein, human