title: Nucleotide Excision Repair: Finely Tuned Molecular Orchestra of Early Pre-incision Events.
abstract: Nucleotide excision repair (NER) eliminates a broad variety of helix-distorting DNA lesions that can otherwise cause genomic instability. NER comprises two distinct subpathways: global genomic NER (GG-NER) operating throughout the genome, and transcription-coupled NER (TC-NER) preferentially removing DNA lesions from transcribing DNA strands of transcriptionally active genes. Several NER factors undergo post-translational modifications, including ubiquitination, occurring swiftly and reversibly at DNA lesion sites. Accumulating evidence indicates that ubiquitination not only orchestrates the spatio-temporal recruitment of key protein factors to DNA lesion sites but also the productive assembly of NER pre-incision complex. This review will be restricted to the latest conceptual understanding of ubiquitin-mediated regulation of initial damage sensors of NER, that is DDB, XPC, RNAPII and CSB. We project hypothetical NER models in which ubiquitin-specific segregase, valosin-containing protein (VCP)/p97, plays an essential role in timely extraction of the congregated DNA damage sensors to functionally facilitate the DNA lesion elimination from the genome.
authors.affiliation: Department of Radiology, The Ohio State University, Columbus, OH.
authors.forename: Qianzheng
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Radiology, The Ohio State University, Columbus, OH.|Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH.|James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH.
authors.forename: Altaf A
authors.initials: AA
authors.lastname: Wani
mesh_terms: D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans; D008962:Models, Theoretical; D000075223:Poly-ADP-Ribose Binding Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012319:RNA Polymerase II / Q000378:metabolism; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination; D000074405:Valosin Containing Protein / Q000378:metabolism
chemical_list: C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D025801:Ubiquitin; C086984:XPC protein, human; D012319:RNA Polymerase II; D004265:DNA Helicases; C078673:ERCC6 protein, human; D000074405:Valosin Containing Protein; D045643:DNA Repair Enzymes