Ubiquitylation-independent degradation of Xeroderma pigmentosum group C protein is required for efficient nucleotide excision repair.
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.
Wang
Qi-En
QE
Department of Radiology, The Ohio State University, 460 W. 12th Ave, Columbus, OH 43210, USA. wang.771@osu.edu
Praetorius-Ibba
Mette
M
Zhu
Qianzheng
Q
El-Mahdy
Mohamed A
MA
Wani
Gulzar
G
Zhao
Qun
Q
Qin
Song
S
Patnaik
Srinivas
S
Wani
Altaf A
AA
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
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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