deficiency in nucleotide excision repair family gene activity, especially ercc3, is associated with non-pigmented hair fiber growth基因的核苷酸切除修复缺陷的家庭活动,尤其是ercc3 non-pigmented头发纤维增长相关联.pdfVIP

Deficiency in Nucleotide Excision Repair Family Gene Activity, Especially ERCC3, Is Associated with Non- Pigmented Hair Fiber Growth 1,2 3,4 1,2 1,2 3,4 4 Mei Yu , Robert H. Bell , Maggie M. Ho , Gigi Leung , Anne Haegert , Nicholas Carr , Jerry Shapiro1, Kevin J. McElwee1,2* 1 Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada, 2 Vancouver Coastal Health Research Institute, Vancouver, Canada, 3 Prostate Centre, Vancouver General Hospital, Vancouver, Canada, 4 Department of Surgery, University of British Columbia, Vancouver, Canada 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 c