title: Melanocyte-stimulating hormone directly enhances UV-Induced DNA repair in keratinocytes by a xeroderma pigmentosum group A-dependent mechanism.
abstract: Melanocyte-stimulating hormone (MSH) reduces UV-induced DNA damage through the induction of pigmentation. In this study, we provide evidence that MSH also enhances DNA repair in skin keratinocytes by modulating the function of DNA repair molecules. Intracutaneous injection of MSH prevented UV-induced DNA damage in human and mouse skin independent of its effects on melanogenesis. In keratinocytes, MSH bound to the melanocyte melanocortin receptor type 1 and activated adenylate cyclase activity, which in turn activated Xeroderma pigmentosum group A (XPA)-binding protein 1 and induced nuclear translocation of XPA, a critical factor controlling nucleotide excision repair signaling pathways. Together, our findings reveal a novel pigmentation-independent mechanism that underlies MSH-mediated DNA repair following UVB irradiation.
authors.affiliation: Department of Pathology, Oncology Institute, Cardinal Bernardin Cancer Center, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.forename: Ji
authors.initials: J
authors.lastname: Wen
authors.forename: Eric
authors.initials: E
authors.lastname: Pier
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Fangzheng
authors.initials: F
authors.lastname: Dong
authors.forename: Nick
authors.initials: N
authors.lastname: Ziegler
authors.forename: Margaret
authors.initials: M
authors.lastname: Mysz
authors.forename: Rafael
authors.initials: R
authors.lastname: Armenta
authors.forename: Rutao
authors.initials: R
authors.lastname: Cui
mesh_terms: D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism; D015398:Signal Transduction; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein / Q000378:metabolism*; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human; D044102:Receptor, Melanocortin, Type 1; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; D000521:alpha-MSH; D000242:Cyclic AMP; C472669:GPN1 protein, human; D019204:GTP-Binding Proteins
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