The melanocortin 1 receptor (MC1R), which signals through cAMP, is a melanocytic transmembrane receptor involved in pigmentation, adaptive tanning, and melanoma resistance. We report MC1R-mediated or pharmacologically-induced cAMP signaling promotes nucleotide excision repair (NER) in a cAMP-dependent protein kinase A (PKA)-dependent manner. PKA directly phosphorylates ataxia telangiectasia and Rad3-related protein (ATR) at Ser435, which actively recruits the key NER protein xeroderma pigmentosum complementation group A (XPA) to sites of nuclear UV photodamage, accelerating clearance of UV-induced photolesions and reducing mutagenesis. Loss of Ser435 within ATR prevents PKA-mediated ATR phosphorylation, disrupts ATR-XPA binding, delays recruitment of XPA to UV-damaged DNA, and elevates UV-induced mutagenesis. This study mechanistically links cAMP-PKA signaling to NER and illustrates potential benefits of cAMP pharmacological rescue to reduce UV mutagenesis in MC1R-defective, melanoma-susceptible individuals.<\/p>\n
PKA-Mediated Phosphorylation of ATR Promotes Recruitment of XPA to UV-Induced DNA Damage<\/a> The melanocortin 1 receptor (MC1R), which signals through cAMP, is a melanocytic transmembrane receptor involved in pigmentation, adaptive tanning, and melanoma resistance. We report MC1R-mediated or pharmacologically-induced cAMP signaling promotes nucleotide excision repair (NER) in a cAMP-dependent protein kinase A (PKA)-dependent manner. PKA directly phosphorylates ataxia telangiectasia and Rad3-related protein (ATR) at Ser435, which actively […]<\/p>\n","protected":false},"author":13,"featured_media":8143,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[730,729,320],"class_list":["post-9042","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-notizie","tag-genetic","tag-melanocortin-1","tag-melanoma"],"_links":{"self":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts\/9042","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/comments?post=9042"}],"version-history":[{"count":1,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts\/9042\/revisions"}],"predecessor-version":[{"id":9043,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts\/9042\/revisions\/9043"}],"wp:attachment":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/media?parent=9042"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/categories?post=9042"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/tags?post=9042"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
\nStuart G. Jarrett, Erin M. Wolf Horrell, Perry A. Christian, Jillian C. Vanover, Mary C. Boulanger, Yue Zou, John A. D\u2019Orazio<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"