Endothelin-1 and α-melanocortin have redundant effects on global genome repair in UV-irradiated human melanocytes despite distinct signaling pathways.

Endothelin-1 and α-melanocortin have redundant effects on global genome repair in UV-irradiated human melanocytes despite distinct signaling pathways. Pigment Cell Melanoma Res. 2019 Sep 10;: Authors: Swope VB, Starner RJ, Rauck C, Abdel-Malek ZA Abstract 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-derived endothelin-1 (End-1) and α-melanocyte stimulating hormone (α-MSH) regulate human melanocyte function, proliferation and survival, and enhance repair of UV-induced DNA photoproducts by binding to the Gq - and Gi -protein coupled endothelin B receptor (EDNRB), and the Gs -protein coupled melanocortin 1 receptor (MC1R), respectively. We hereby report that End-1 and α-MSH 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-related and ataxia telangiectasia mutated, enhance DNA damage recognition by reducing soluble nuclear and chromatin bound DNA damage binding protein 2, and increase total and chromatin bound xeroderma pigmentosum (XP) C. Additionally, α-MSH and End-1 increase total levels and chromatin localization of the damage verification protein XPA, and the levels of γH2AX, which facilitates recruitment of DNA repair proteins to DNA lesions. Activation of EDN...
Source: Pigment Cell and Melanoma Research - Category: Cytology Authors: Tags: Pigment Cell Melanoma Res Source Type: research