Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Atypical UV Photoproducts Induce Non-canonical Mutation Classes Associated with Driver Mutations in Melanoma.

Authors: Laughery, Marian F; Brown, Alexander J; Bohm, Kaitlynne A; Sivapragasam, Smitha; Morris, Haley S; Tchmola, Mila; Washington, Angelica D; Mitchell, Debra; Mather, Stephen; Malc, Ewa P; Mieczkowski, Piotr A; Roberts, Steven A; Wyrick, John J

Published In Cell Rep, (2020 11 17)

Abstract: Somatic mutations in skin cancers and other ultraviolet (UV)-exposed cells are typified by C>T and CC>TT substitutions at dipyrimidine sequences; however, many oncogenic "driver" mutations in melanoma do not fit this UV signature. Here, we use genome sequencing to characterize mutations in yeast repeatedly irradiated with UV light. Analysis of ~50,000 UV-induced mutations reveals abundant non-canonical mutations, including T>C, T>A, and AC>TT substitutions. These mutations display transcriptional asymmetry that is modulated by nucleotide excision repair (NER), indicating that they are caused by UV photoproducts. Using a sequencing method called UV DNA endonuclease sequencing (UVDE-seq), we confirm the existence of an atypical thymine-adenine photoproduct likely responsible for UV-induced T>A substitutions. Similar non-canonical mutations are present in skin cancers, which also display transcriptional asymmetry and dependence on NER. These include multiple driver mutations, most prominently the recurrent BRAF V600E and V600K substitutions, suggesting that mutations arising from rare, atypical UV photoproducts may play a role in melanomagenesis.

PubMed ID: 33207206 Exiting the NIEHS site

MeSH Terms: Base Sequence/genetics; DNA Damage/genetics; DNA Repair/genetics; Melanoma/genetics*; Melanoma/metabolism; Mutation/genetics; Mutation/radiation effects*; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Sequence Analysis, DNA/methods; Ultraviolet Rays/adverse effects*

to Top