Deficiency in Nucleotide Excision Repair Family Gene Activity, Especially ERCC3, is Associated with Non-pigmented Hair Fiber Growth

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 May 23

PMID 22615732

Citations 6

Authors

Mei Yu

Robert H Bell

Maggie M Ho

Gigi Leung

Anne Haegert

Nicholas Carr

Jerry Shapiro

Kevin J McElwee

Affiliations

Soon will be listed here.

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.

Citing Articles

Comprehensive analysis of lncRNAs modified by m6A methylation in sheep skin.

Meng J, Li J, Zhao Y Anim Biosci. 2024; 37(11):1887-1990.

PMID: 38754841 PMC: 11541038. DOI: 10.5713/ab.24.0039.

Irradiation-induced hair graying in mice: an experimental model to evaluate the effectiveness of interventions targeting oxidative stress, DNA damage prevention, and cellular senescence.

Ungvari A, Kiss T, Gulej R, Tarantini S, Csik B, Yabluchanskiy A Geroscience. 2024; 46(3):3105-3122.

PMID: 38182857 PMC: 11009199. DOI: 10.1007/s11357-023-01042-7.

Whole-Genome Resequencing Reveals Selection Signal Related to Sheep Wool Fineness.

Zhang W, Jin M, Li T, Lu Z, Wang H, Yuan Z Animals (Basel). 2023; 13(18).

PMID: 37760343 PMC: 10526036. DOI: 10.3390/ani13182944.

Stress-sensing in the human greying hair follicle: Ataxia Telangiectasia Mutated (ATM) depletion in hair bulb melanocytes in canities-prone scalp.

Sikkink S, Mine S, Freis O, Danoux L, Tobin D Sci Rep. 2020; 10(1):18711.

PMID: 33128003 PMC: 7603349. DOI: 10.1038/s41598-020-75334-9.

Genomic footprints of dryland stress adaptation in Egyptian fat-tail sheep and their divergence from East African and western Asia cohorts.

Mwacharo J, Kim E, Elbeltagy A, Aboul-Naga A, Rischkowsky B, Rothschild M Sci Rep. 2017; 7(1):17647.

PMID: 29247174 PMC: 5732286. DOI: 10.1038/s41598-017-17775-3.

References

Slominski A, Tobin D, Shibahara S, Wortsman J . Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev. 2004; 84(4):1155-228. DOI: 10.1152/physrev.00044.2003. View

Kapur R, Bigler S, Skelly M, Gown A . Anti-melanoma monoclonal antibody HMB45 identifies an oncofetal glycoconjugate associated with immature melanosomes. J Histochem Cytochem. 1992; 40(2):207-12. DOI: 10.1177/40.2.1552165. View

Nishimura E, Granter S, Fisher D . Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science. 2004; 307(5710):720-4. DOI: 10.1126/science.1099593. View

Slominski A, Paus R . Melanogenesis is coupled to murine anagen: toward new concepts for the role of melanocytes and the regulation of melanogenesis in hair growth. J Invest Dermatol. 1993; 101(1 Suppl):90S-97S. DOI: 10.1111/1523-1747.ep12362991. View

Arck P, Overall R, Spatz K, Liezman C, Handjiski B, Klapp B . Towards a "free radical theory of graying": melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage. FASEB J. 2006; 20(9):1567-9. DOI: 10.1096/fj.05-4039fje. View

Beck B, Hah D, Lee S . XPB and XPD between transcription and DNA repair. Adv Exp Med Biol. 2009; 637:39-46. DOI: 10.1007/978-0-387-09599-8_5. View

Green M, Karp P . The outcomes of pathway database computations depend on pathway ontology. Nucleic Acids Res. 2006; 34(13):3687-97. PMC: 1540720. DOI: 10.1093/nar/gkl438. View

Passeron T, Coelho S, Miyamura Y, Takahashi K, Hearing V . Immunohistochemistry and in situ hybridization in the study of human skin melanocytes. Exp Dermatol. 2007; 16(3):162-70. DOI: 10.1111/j.1600-0625.2006.00538.x. View

Stenn K, Paus R . Controls of hair follicle cycling. Physiol Rev. 2001; 81(1):449-494. DOI: 10.1152/physrev.2001.81.1.449. View

10.

van Neste D, Tobin D . Hair cycle and hair pigmentation: dynamic interactions and changes associated with aging. Micron. 2004; 35(3):193-200. DOI: 10.1016/j.micron.2003.11.006. View

11.

Tusher V, Tibshirani R, Chu G . Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001; 98(9):5116-21. PMC: 33173. DOI: 10.1073/pnas.091062498. View

12.

Kim D, Hwang E, Lee J, Kim S, Kwon S, Park K . Sphingosine-1-phosphate decreases melanin synthesis via sustained ERK activation and subsequent MITF degradation. J Cell Sci. 2003; 116(Pt 9):1699-706. DOI: 10.1242/jcs.00366. View

13.

Rabbani P, Takeo M, Chou W, Myung P, Bosenberg M, Chin L . Coordinated activation of Wnt in epithelial and melanocyte stem cells initiates pigmented hair regeneration. Cell. 2011; 145(6):941-955. PMC: 3962257. DOI: 10.1016/j.cell.2011.05.004. View

14.

Andressoo J, Weeda G, de Wit J, Mitchell J, Beems R, van Steeg H . An Xpb mouse model for combined xeroderma pigmentosum and cockayne syndrome reveals progeroid features upon further attenuation of DNA repair. Mol Cell Biol. 2008; 29(5):1276-90. PMC: 2643825. DOI: 10.1128/MCB.01229-08. View

15.

Steingrimsson E, Copeland N, Jenkins N . Melanocyte stem cell maintenance and hair graying. Cell. 2005; 121(1):9-12. DOI: 10.1016/j.cell.2005.03.021. View

16.

Isken O, Maquat L . The multiple lives of NMD factors: balancing roles in gene and genome regulation. Nat Rev Genet. 2008; 9(9):699-712. PMC: 3711694. DOI: 10.1038/nrg2402. View

17.

Commo S, Bernard B . Melanocyte subpopulation turnover during the human hair cycle: an immunohistochemical study. Pigment Cell Res. 2000; 13(4):253-9. DOI: 10.1034/j.1600-0749.2000.130407.x. View

18.

Mitchell J, Hoeijmakers J, Niedernhofer L . Divide and conquer: nucleotide excision repair battles cancer and ageing. Curr Opin Cell Biol. 2003; 15(2):232-40. DOI: 10.1016/s0955-0674(03)00018-8. View

19.

Yu M, Zloty D, Cowan B, Shapiro J, Haegert A, Bell R . Superficial, nodular, and morpheiform basal-cell carcinomas exhibit distinct gene expression profiles. J Invest Dermatol. 2008; 128(7):1797-805. DOI: 10.1038/sj.jid.5701243. View

20.

Tobin D, Hordinsky M, Bernard B . Hair pigmentation: a research update. J Investig Dermatol Symp Proc. 2005; 10(3):275-9. DOI: 10.1111/j.1087-0024.2005.10117.x. View