AUTHOR=Bohm Kaitlynne A. , Wyrick John J. 

TITLE=Damage mapping techniques and the light they have shed on canonical and atypical UV photoproducts

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.1102593

DOI=10.3389/fgene.2022.1102593

ISSN=1664-8021

ABSTRACT=<p>Ultraviolet (UV) light is a pervasive threat to the DNA of terrestrial organisms. UV light induces helix-distorting DNA lesions, primarily cyclobutane pyrimidine dimers (CPDs) that form between neighboring pyrimidine bases. Unrepaired CPD lesions cause cytosine-to-thymine (C&gt;T) substitutions in dipyrimidine sequences, which is the predominant mutation class in skin cancer genomes. However, many driver mutations in melanoma (<italic>e.g.,</italic> in the <italic>BRAF</italic> and <italic>NRAS</italic> oncogenes) do not fit this UV mutation signature. Recent studies have brought to light the intriguing hypothesis that these driver mutations may be induced by infrequent or atypical UV photoproducts, including pyrimidine 6-4 pyrimidone photoproducts (6-4PP) and thymine-adenine (TA) photoproducts. Here, we review innovative methods for mapping both canonical and atypical UV-induced photoproducts across the genome.</p>