{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:16:12Z","timestamp":1790878572572,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P30ES006096"],"award-info":[{"award-number":["P30ES006096"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01 ES017561"],"award-info":[{"award-number":["R01 ES017561"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human melanocyte homeostasis is sustained by paracrine factors that reduce the genotoxic effects of ultraviolet radiation (UV), the major etiological factor for melanoma. The keratinocyte\u2010derived endothelin\u20101 (End\u20101) and \u03b1\u2010melanocyte\u2010stimulating hormone (\u03b1\u2010MSH) regulate human melanocyte function, proliferation and survival, and enhance repair of UV\u2010induced DNA photoproducts by binding to the G<jats:sub>q<\/jats:sub>\u2010 and G<jats:sub>i<\/jats:sub>\u2010protein\u2010coupled endothelin B receptor (EDNRB), and the G<jats:sub>s<\/jats:sub>\u2010protein\u2010coupled melanocortin 1 receptor (MC1R), respectively. We hereby report that End\u20101 and \u03b1\u2010MSH regulate common effectors of the DNA damage response to UV, despite distinct signaling pathways. Both factors activate the two DNA damage sensors ataxia telangiectasia and Rad3\u2010related and ataxia telangiectasia mutated, enhance DNA damage recognition by reducing soluble nuclear and chromatin\u2010bound DNA damage binding protein 2, and increase total and chromatin\u2010bound xeroderma pigmentosum (XP) C. Additionally, \u03b1\u2010MSH and End\u20101 increase total levels and chromatin localization of the damage verification protein XPA, and the levels of \u03b3H2AX, which facilitates recruitment of DNA repair proteins to DNA lesions. Activation of EDNRB compensates for MC1R loss of function, thereby reducing the risk of malignant transformation of these vulnerable melanocytes. Therefore, MC1R and EDNRB signaling pathways represent redundant mechanisms that inhibit the genotoxic effects of UV and melanomagenesis.<\/jats:p>","DOI":"10.1111\/pcmr.12823","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T18:44:43Z","timestamp":1568141083000},"page":"293-304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Endothelin\u20101 and \u03b1\u2010melanocortin have redundant effects on global genome repair in UV\u2010irradiated human melanocytes despite distinct signaling pathways"],"prefix":"10.1111","volume":"33","author":[{"given":"Viki B.","family":"Swope","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Cincinnati Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renny J.","family":"Starner","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Cincinnati Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Rauck","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Cincinnati Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2651-1533","authenticated-orcid":false,"given":"Zalfa A.","family":"Abdel\u2010Malek","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Cincinnati Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.5.1789"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801585105"},{"key":"e_1_2_7_4_1","first-page":"4041","article-title":"Comparison of the responses of human melanocytes with different melanin contents to ultraviolet B irradiation","volume":"55","author":"Barker D.","year":"1995","journal-title":"Cancer Research"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406334200"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/157016107779317161"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.11.1891"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0216-1"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069398"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(96)00063-8"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2450"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002175107"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.426"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05098"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2014.12.002"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.024"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199904293401707"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02623492"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm157"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2006.00315.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.06.024"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)35817-4"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.003940"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.05.030"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.280"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.391"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-11-0436"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-4535"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-158485"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.1994.tb00703.x"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2359"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.539"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms13010142"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1086\/302711"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17111840"},{"key":"e_1_2_7_36_1","first-page":"655","volume-title":"Phenotypic expression in pigment cells","author":"Pathak M. 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