Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure

Sanjay Premi 1 Silvia Wallisch 1 Camila M. Mano 1 Adam B. Weiner 1 Antonella Bacchiocchi 1 Kazumasa Wakamatsu 2 Etelvino J. H. Bechara 3 Ruth Halaban 4 Thierry Douki 5 Douglas E. Brash 1
1 Yale University School of Medicine
2 Sch Hlth Sci, Dept Chem
3 USP - Universidade de São Paulo
4 Department of Dermatology
5 LAN - Laboratoire Lésions des Acides Nucléiques
SCIB - UMR E3 - Service de Chimie Inorganique et Biologique : DSM/INAC/SCIB
Abstract : Mutations in sunlight-induced melanoma arise from cyclobutane pyrimidine dimers (CPDs), DNA photoproducts that are typically created picoseconds after an ultraviolet (UV) photon is absorbed at thymine or cytosine. We found that in melanocytes, CPDs are generated for > 3 hours after exposure to UVA, a major component of the radiation in sunlight and in tanning beds. These "dark CPDs" constitute the majority of CPDs and include the cytosine-containing CPDs that initiate UV-signature C -> T mutations. Dark CPDs arise when UV-induced reactive oxygen and nitrogen species combine to excite an electron in fragments of the pigment melanin. This creates a quantum triplet state that has the energy of a UV photon but induces CPDs by energy transfer to DNA in a radiation-independent manner. Melanin may thus be carcinogenic as well as protective against cancer. These findings also validate the long-standing suggestion that chemically generated excited electronic states are relevant to mammalian biology.
Keywords : Ultraviolet Skin Keratinocytes Pheomelanin
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Journal articles
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https://hal-cea.archives-ouvertes.fr/cea-01735136
Contributor : Jérôme Planès <>
Submitted on : Thursday, March 15, 2018 - 2:57:50 PM
Last modification on : Friday, July 26, 2019 - 3:22:31 PM

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Sanjay Premi, Silvia Wallisch, Camila M. Mano, Adam B. Weiner, Antonella Bacchiocchi, et al.. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science, American Association for the Advancement of Science, 2015, 347 (6224), pp.842-847. ⟨10.1126/science.1256022⟩. ⟨cea-01735136⟩

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