{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:12:51Z","timestamp":1789150371448,"version":"build-2803163510"},"reference-count":63,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"37","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 ES032814"],"award-info":[{"award-number":["R01 ES032814"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 ES032814"],"award-info":[{"award-number":["R01 ES032814"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["3P30CA016086-49S1"],"award-info":[{"award-number":["3P30CA016086-49S1"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:p>\n                    Persistence of common ultraviolet (UV)\u2013induced lesions, like cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (6-4-PPs), typically results in C&gt;T substitutions at dipyrimidines: a mutation pattern that composes the single-base substitution (SBS) signature 7 in cancer. Oncogenic melanoma mutations rarely involve SBS7-like substitutions. We recently identified noncanonical UV-induced mutations in yeast that appear to originate from atypical AC and TA photoproducts. While an AC photoproduct could account for formation of BRAF V600K, other melanoma drivers like BRAF V600E and NRAS Q61K involve other mutation types, suggesting possible existence of additional atypical photoproducts. Here, we couple temperature-induced telomeric end resection in yeast with serial UV irradiation and whole-genome sequencing to show UV light induces an extended array of noncanonical mutations in single-stranded DNA (ssDNA). This includes A\n                    <jats:underline>T<\/jats:underline>\n                    &gt;A\n                    <jats:underline>M<\/jats:underline>\n                    , G\n                    <jats:underline>T<\/jats:underline>\n                    &gt;G\n                    <jats:underline>V<\/jats:underline>\n                    , A\n                    <jats:underline>C<\/jats:underline>\n                    &gt;A\n                    <jats:underline>A<\/jats:underline>\n                    ,\n                    <jats:underline>A<\/jats:underline>\n                    T&gt;\n                    <jats:underline>T<\/jats:underline>\n                    T, and T\n                    <jats:underline>A<\/jats:underline>\n                    &gt;T\n                    <jats:underline>T<\/jats:underline>\n                    substitutions that are resistant to photo-reversion, indicating that they likely originate from atypical photoproducts. UV-induced mutation spectra in yeast lacking Rad30 indicated that Pol \u03b7 plays substantial roles in the bypass of CPDs and 6-4-PPs regardless of telomere proximity. Unexpectedly, expression of a mutant DNA pol \u03b5 (pol2 M644G) reduced both canonical and noncanonical UV-induced mutations specifically within subtelomeric regions of the genome. This suggests a preferential role for pol \u03b5 in the resynthesis of uncapped telomeres, with the M644G mutation conferring accurate lesion bypass capabilities to the replicative polymerase. ssDNA-specific UV lesions provide additional damage-mediated mechanisms for the production of oncogenic mutations in melanoma, such as the BRAF V600E mutation that involves a G\n                    <jats:underline>T<\/jats:underline>\n                    &gt;G\n                    <jats:underline>A<\/jats:underline>\n                    substitution.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeg5184","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:58:29Z","timestamp":1789149509000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Widespread atypical UV-induced mutations form in single-stranded DNA"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8320-0953","authenticated-orcid":true,"given":"Cameron","family":"Cordero","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2630-0100","authenticated-orcid":true,"given":"Brittany N.","family":"Vandenberg","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA."},{"name":"School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7283-8411","authenticated-orcid":true,"given":"Isabelle","family":"Mittelstadt","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1687-6357","authenticated-orcid":true,"given":"Jordan","family":"Murch","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian F.","family":"Laughery","sequence":"additional","affiliation":[{"name":"School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2418-0096","authenticated-orcid":true,"given":"Piotr A.","family":"Mieczkowski","sequence":"additional","affiliation":[{"name":"Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7911-3803","authenticated-orcid":true,"given":"John J.","family":"Wyrick","sequence":"additional","affiliation":[{"name":"School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3628-5808","authenticated-orcid":true,"given":"Steven A.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA."},{"name":"School of Molecular Biosciences, Washington State University, Pullman, WA 99164, 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Roberts Code for: Widespread atypical UV-induced mutations form in single-stranded DNA version v1.3 Zenodo (2026); https:\/\/doi.org\/10.5281\/zenodo.20705714."}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aeg5184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:59:25Z","timestamp":1789149565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aeg5184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":63,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2026,9,11]]}},"alternative-id":["10.1126\/sciadv.aeg5184"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aeg5184","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"assertion":[{"value":"2026-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaeg5184"}}