The Dark Side of Melanin

Researchers uncover a previously unknown way UV light can act on melanin, spurring cancer-causing mutations hours after sun exposure.

Written byAnna Azvolinsky
| 3 min read

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MITF immunostaining highlights malignant human melanocytesCASES JOURNAL, S. REPERTINGER ET AL.In 1971, Angelo Lamola—who was then at Bell Laboratories—used an unusual chemical, trimethyldioxetane, to produce DNA lesions in a test tube. Decades later, the same lesions, produced by sunlight, were linked to melanoma, an aggressive type of skin cancer. Now, researchers at Yale University and their colleagues have found that this reaction occurs in the skin cells of mice hours after ultraviolet (UV) light exposure. The team’s results are published today (February 19) in Science.

“The study is really interesting and provocative,” said David Fisher, a cancer biologist focusing on melanoma at Massachusetts General Hospital in Boston who was not involved in the work. “It underlines even more than what we knew previously: that melanin biochemistry is a two-edged sword—there are benefits and liabilities.”

UV light acts directly on DNA to form cyclobutane pyrimidine dimers (CPDs) within picoseconds, which, if not repaired, subsequently result in a mutation—a cytosine-to-thymine change. Most melanomas stem from these fast-forming CPDs that linger and lead to mutations.

Yale biophysicist Douglas Brash and his colleagues were doing time course experiments after irradiating murine melanocytes—the cells in the skin that produce melanin pigments and in which most melanomas arise—and stumbled onto an unusual observation: the melanocytes continued ...

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    Anna Azvolinsky received a PhD in molecular biology in November 2008 from Princeton University. Her graduate research focused on a genome-wide analyses of genomic integrity and DNA replication. She did a one-year post-doctoral fellowship at Memorial Sloan Kettering Cancer Center in New York City and then left academia to pursue science writing. She has been a freelance science writer since 2012, based in New York City.

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