title: Deficiency in nucleotide excision repair family gene activity, especially ERCC3, is associated with non-pigmented hair fiber growth.
abstract: We conducted a microarray study to discover gene expression patterns associated with a lack of melanogenesis in non-pigmented hair follicles (HF) by microarray. Pigmented and non-pigmented HFs were collected and micro-dissected into the hair bulb (HB) and the upper hair sheaths (HS) including the bulge region. In comparison to pigmented HS and HBs, nucleotide excision repair (NER) family genes ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, XPA, NTPBP, HCNP, DDB2 and POLH exhibited statistically significantly lower expression in non- pigmented HS and HBs. Quantitative PCR verified microarray data and identified ERCC3 as highly differentially expressed. Immunohistochemistry confirmed ERCC3 expression in HF melanocytes. A reduction in ERCC3 by siRNA interference in human melanocytes in vitro reduced their tyrosinase production ability. Our results suggest that loss of NER gene function is associated with a loss of melanin production capacity. This may be due to reduced gene transcription and/or reduced DNA repair in melanocytes which may eventually lead to cell death. These results provide novel information with regard to melanogenesis and its regulation.
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada.
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bell
authors.forename: Maggie M
authors.initials: MM
authors.lastname: Ho
authors.forename: Gigi
authors.initials: G
authors.lastname: Leung
authors.forename: Anne
authors.initials: A
authors.lastname: Haegert
authors.forename: Nicholas
authors.initials: N
authors.lastname: Carr
authors.forename: Jerry
authors.initials: J
authors.lastname: Shapiro
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: McElwee
mesh_terms: D002478:Cells, Cultured; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D006197:Hair / Q000737:chemistry*; D006801:Humans; D008544:Melanocytes / Q000166:cytology*; D034741:RNA, Small Interfering
chemical_list: D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C072022:XPBC-ERCC-3 protein; D004265:DNA Helicases