Journal
CANCER RESEARCH
Volume 70, Issue 9, Pages 3547-3556Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-09-4596
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Funding
- NIH [1RO1CA137098]
- American Cancer Society [RSG-09-022-01-CNE]
- American Cancer Society-Illinois Division [08-026]
- Elsa U. Pardee Foundation
- The Harry J. Lloyd Charitable Trust
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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.
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