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.
Dong
Liang
L
Department of Pathology, Oncology Institute, Cardinal Bernardin Cancer Center, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA.
Wen
Ji
J
Pier
Eric
E
Zhang
Xiao
X
Zhang
Bo
B
Dong
Fangzheng
F
Ziegler
Nick
N
Mysz
Margaret
M
Armenta
Rafael
R
Cui
Rutao
R
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*
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
Nature. 2002 Apr 25;416(6883):854-60
11976685
Cancer Res. 2006 Mar 15;66(6):2997-3005
16540648
Photochem Photobiol. 1996 Jan;63(1):1-10
8577860
Photodermatol Photoimmunol Photomed. 1997 Feb-Apr;13(1-2):64-6
9361131
J Biol Chem. 2005 Feb 18;280(7):5795-802
15569680
Front Biosci. 2002 Apr 01;7:d1024-43
11897551
FASEB J. 2006 Jul;20(9):1561-3
16723376
Mutat Res. 2005 Sep 4;577(1-2):77-91
15923014
Nat Genet. 1998 Jun;19(2):155-7
9620771
Oncogene. 2007 Feb 1;26(5):757-64
16862173
Nature. 2006 Sep 21;443(7109):340-4
16988713
Biochim Biophys Acta. 1996 Aug 28;1313(2):130-8
8781560
Pigment Cell Melanoma Res. 2009 Oct;22(5):635-44
19558415
J Invest Dermatol. 2009 Jan;129(1):162-6
18580960
J Am Acad Dermatol. 1979 Sep;1(3):249-60
512075
Peptides. 2006 Feb;27(2):388-94
16293341
Biofactors. 2009 Mar-Apr;35(2):193-9
19449448
J Invest Dermatol. 1996 Sep;107(3):332-5
8751966
J Am Acad Dermatol. 1993 Dec;29(6):959-62
8245261
Peptides. 2006 Feb;27(2):444-52
16274844
Endocrinology. 2009 Jul;150(7):3197-206
19282378
Nat Rev Mol Cell Biol. 2003 May;4(5):361-72
12728270
Arch Dermatol Res. 1982;273(3-4):301-6
6762159
Photochem Photobiol. 1997 Feb;65(2):270-83
9066304
Nucleic Acids Res. 2000 Nov 1;28(21):4212-8
11058119
Science. 1998 Dec 18;282(5397):2275-9
9856955
J Am Acad Dermatol. 1983 Nov;9(5):724-33
6358278
Nat Struct Mol Biol. 2006 Mar;13(3):278-84
16491090
Nature. 1993 Apr 29;362(6423):847-9
8479522
Endocrinology. 1984 Mar;114(3):761-6
6321138
Exp Dermatol. 1999 Dec;8(6):453-61
10597134
J Invest Dermatol. 1996 Jan;106(1):3-10
8592078
Photochem Photobiol. 2008 Mar-Apr;84(2):501-8
18282187
J Biol Chem. 2002 May 3;277(18):16096-101
11859086
Biochim Biophys Acta. 2008 Jan;1784(1):16-26
17996741
J Investig Dermatol Symp Proc. 1997 Aug;2(1):87-93
9487022
J Invest Dermatol. 1999 Jun;112(6):853-60
10383729
Antioxid Redox Signal. 2005 Nov-Dec;7(11-12):1664-73
16356128
Cell. 2007 Mar 9;128(5):853-64
17350573
Gene. 2001 May 16;269(1-2):13-25
11376933
Endocr Rev. 2000 Oct;21(5):457-87
11041445
Biochimie. 1999 Jan-Feb;81(1-2):39-44
10214908
Nature. 1992 Jul 2;358(6381):83-6
1614538
Pigment Cell Res. 1996 Aug;9(4):179-84
8948499
Annu Rev Biochem. 2004;73:39-85
15189136
Peptides. 2005 Oct;26(10):1965-71
15963603
Cancer Res. 2005 May 15;65(10):4292-9
15899821
Proc Natl Acad Sci U S A. 1989 Jul;86(14):5512-6
2748601
J Physiol. 2007 Oct 1;584(Pt 1):191-203
17702820