title: Paracrine regulation of melanocyte genomic stability: a focus on nucleotide excision repair.
abstract: UV radiation is a major environmental risk factor for the development of melanoma by causing DNA damage and mutations. Resistance to UV damage is largely determined by the capacity of melanocytes to respond to UV injury by repairing mutagenic photolesions. The nucleotide excision repair (NER) pathway is the major mechanism by which cells correct UV photodamage. This multistep process involves the basic steps of damage recognition, isolation, localized strand unwinding, assembly of a repair complex, excision of the damage-containing strand 3' and 5' to the photolesion, synthesis of a sequence-appropriate replacement strand, and finally ligation to restore continuity of genomic DNA. In melanocytes, the efficiency of NER is regulated by several hormonal pathways including the melanocortin and endothelin signaling pathways. Elucidating molecular mechanisms by which melanocyte DNA repair is regulated offers the possibility of developing novel melanoma-preventive strategies to reduce UV mutagenesis, especially in UV-sensitive melanoma-prone individuals.
authors.affiliation: Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, USA.|Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Stuart Gordon
authors.initials: SG
authors.lastname: Jarrett
authors.affiliation: Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Katharine Marie
authors.initials: KM
authors.lastname: Carter
authors.affiliation: Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, USA.|Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY, USA.|Department of Physiology, University of Kentucky College of Medicine, Lexington, KY, USA.|Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA.|Department of Pediatrics, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: John August
authors.identifier: 0000-0003-1008-6234
authors.initials: JA
authors.lastname: D'Orazio
mesh_terms: D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D042822:Genomic Instability / Q000528:radiation effects; D006801:Humans; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D019899:Paracrine Communication / Q000528:radiation effects; D014466:Ultraviolet Rays
keywords: UV photodamage; endothelin receptor signaling; melanocortin signaling; mutagenesis; nucleotide excision repair