Sep 11, 2019

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

Pigment Cell & Melanoma Research
Viki B SwopeZalfa Abdel-Malek

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 EDNRB compensates for MC1R loss of function, thereby re...Continue Reading

  • References49
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References

  • References49
  • Citations1

Citations

Mentioned in this Paper

EDNRB
Melanocyte
XPA gene
MC1R Protein
Genome
G-Protein-Coupled Receptors
Response to DNA Damage Stimulus
UVH6 protein, Arabidopsis
Cell Proliferation
Endothelin-1

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