Melanocyte-Stimulating Hormone Directly Enhances UV-Induced DNA Repair in Keratinocytes by a Xeroderma Pigmentosum Group A-Dependent Mechanism

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. Cancer Res; 70(9); 3547-56. (C) 2010 AACR.