title: Impaired nucleotide excision repair upon macrophage differentiation is corrected by E1 ubiquitin-activating enzyme.
abstract: Global nucleotide excision repair is greatly attenuated in terminally differentiated mammalian cells. We observed this phenomenon in human neurons and in macrophages, noting that the transcription-coupled repair pathway remains functional and that there is no significant reduction in levels of excision repair enzymes. We have discovered that ubiquitin-activating enzyme E1 complements the repair deficiency in macrophage extracts, and although there is no reduction in the concentration of E1 upon differentiation, our results indicate a reduction in phosphorylation of E1. In preliminary studies, we have identified the basal transcription factor TFIIH as the potential target for ubiquitination. We suggest that this unusual type of regulation at the level of the E1 enzyme is likely to affect numerous cellular processes and may represent a strategy to coordinate multiple phenotypic changes upon differentiation by using E1 as a "master switch."
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.
authors.forename: Thierry
authors.initials: T
authors.lastname: Nouspikel
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hanawalt
mesh_terms: D002454:Cell Differentiation; D002457:Cell Extracts; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D003165:Complement System Proteins / Q000302:isolation & purification / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism*; D014983:Xeroderma Pigmentosum / Q000235:genetics
chemical_list: D002457:Cell Extracts; D003165:Complement System Proteins; D004247:DNA; D044764:Ubiquitin-Activating Enzymes; D002945:Cisplatin