title: Ubiquitylation-independent degradation of Xeroderma pigmentosum group C protein is required for efficient nucleotide excision repair.
abstract: The Xeroderma Pigmentosum group C (XPC) protein is indispensable to global genomic repair (GGR), a subpathway of nucleotide excision repair (NER), and plays an important role in the initial damage recognition. XPC can be modified by both ubiquitin and SUMO in response to UV irradiation of cells. Here, we show that XPC undergoes degradation upon UV irradiation, and this is independent of protein ubiquitylation. The subunits of DDB-Cul4A E3 ligase differentially regulate UV-induced XPC degradation, e.g DDB2 is required and promotes, whereas DDB1 and Cul4A protect the protein degradation. Mutation of XPC K655 to alanine abolishes both UV-induced XPC modification and degradation. XPC degradation is necessary for recruiting XPG and efficient NER. The overall results provide crucial insights regarding the fate and role of XPC protein in the initiation of excision repair.
authors: Department of Radiology, The Ohio State University, 460 W. 12th Ave, Columbus, OH 43210, USA. wang.771@osu.edu
authors: Qi-En
authors: QE
authors: Wang
authors: Mette
authors: M
authors: Praetorius-Ibba
authors: Qianzheng
authors: Q
authors: Zhu
authors: Mohamed A
authors: MA
authors: El-Mahdy
authors: Gulzar
authors: G
authors: Wani
authors: Qun
authors: Q
authors: Zhao
authors: Song
authors: S
authors: Qin
authors: Srinivas
authors: S
authors: Patnaik
authors: Altaf A
authors: AA
authors: Wani
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D044842:Cullin Proteins / Q000502:physiology; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D004720:Endonucleases / Q000378:metabolism; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D014466:Ultraviolet Rays; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D044842:Cullin Proteins; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D000099250:DNA Excision Repair Protein ERCC-5; C114234:CUL4A protein, human; C091435:DDB1 protein, human; C117669:DDB2 protein, human; C086984:XPC protein, human
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