title: A human XPC protein interactome--a resource.
abstract: Global genome nucleotide excision repair (GG-NER) is responsible for identifying and removing bulky adducts from non-transcribed DNA that result from damaging agents such as UV radiation and cisplatin. Xeroderma pigmentosum complementation group C (XPC) is one of the essential damage recognition proteins of the GG-NER pathway and its dysfunction results in xeroderma pigmentosum (XP), a disorder involving photosensitivity and a predisposition to cancer. To better understand the identification of DNA damage by XPC in the context of chromatin and the role of XPC in the pathogenesis of XP, we characterized the interactome of XPC using a high throughput yeast two-hybrid screening. Our screening showed 49 novel interactors of XPC involved in DNA repair and replication, proteolysis and post-translational modifications, transcription regulation, signal transduction, and metabolism. Importantly, we validated the XPC-OTUD4 interaction by co-IP and provided evidence that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by cleaving the ubiquitin moiety. This high-throughput characterization of the XPC interactome provides a resource for future exploration and suggests that XPC may have many uncharacterized cellular functions.
authors.forename: Abigail
authors.initials: A
authors.lastname: Lubin
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.forename: Victoria M
authors.initials: VM
authors.lastname: White
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33156, USA. fgong@med.miami.edu.
authors.forename: Feng
authors.initials: F
authors.lastname: Gong
mesh_terms: D004260:DNA Repair; D045325:HCT116 Cells; D006801:Humans; D060066:Protein Interaction Maps; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017422:Sequence Analysis, DNA; D020798:Two-Hybrid System Techniques; D064570:Ubiquitin-Specific Proteases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination; D014983:Xeroderma Pigmentosum / Q000737:chemistry / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D064570:Ubiquitin-Specific Proteases