title: RB stabilizes XPC and promotes cellular NER.
abstract: It has long been thought that the G(1)/S cell cycle checkpoint allows time for DNA repair by delaying S-phase entry. The p53 tumor suppressor pathway regulates the G(1)/S checkpoint by regulating the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), but p53 also regulates the nucleotide excision DNA repair protein XPC. Here, using p53-null cell lines we show that additional mechanisms stabilize XPC protein and promote nucleotide excision repair (NER) in concert with the G(1)/S checkpoint. At least one mechanism to stabilize and destabilize XPC involves ubiquitin-mediated degradation of XPC, as the ubiquitin ligase inhibitor MG-132 blocked XPC degradation. The retinoblastoma protein RB, in its unphosphorylated form actually stabilized XPC and promoted NER as measured by host cell reactivation experiments. The data suggest that XPC protein and XPC-mediated NER are tightly linked to the G(1)/S checkpoint, even in cells lacking functional p53.
authors.affiliation: Department of Microbiology, Indiana University School of Medicine, IN 46202, USA.
authors.forename: Tabitha M
authors.initials: TM
authors.lastname: Hardy
authors.forename: Ma Suresh
authors.initials: MS
authors.lastname: Kumar
authors.forename: Martin L
authors.initials: ML
authors.lastname: Smith
mesh_terms: D000483:Alleles; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D019927:Cyclin E / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids / Q000235:genetics; D025941:Protein Interaction Mapping; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection
chemical_list: D019927:Cyclin E; D004268:DNA-Binding Proteins; D016160:Retinoblastoma Protein; C086984:XPC protein, human