{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T08:39:50Z","timestamp":1786523990141,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM148186"],"award-info":[{"award-number":["R35 GM148186"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R35 GM148186"],"award-info":[{"award-number":["R35 GM148186"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Translesion synthesis is a major DNA damage bypass pathway in which specialized DNA polymerases, such as pol \u03b7 and Rev1, are recruited to stalled replication forks where they catalyze nucleotide incorporation opposite DNA damage. Translesion synthesis is regulated by the Rad6-Rad18 complex, which catalyzes PCNA mono-ubiquitylation. Despite its central role in regulating translesion synthesis, its oligomeric state and molecular interactions are poorly understood. Here, we use mass photometry to show that Rad18 co-purifies with Rad6 and forms a series of larger oligomeric complexes. Using yeast two-hybrid studies, we showed that while the full-length Rad18 complex interacts with pol \u03b7, its interaction with Rev1 is controlled by auto-inhibition. The release of this auto-inhibition is associated with the dissociation of the Rad6-Rad18 complex, freeing Rad18 monomers and dimers. Because pol \u03b7 participates in non-mutagenic translesion synthesis, while Rev1 participates in mutagenic translesion synthesis, this auto-inhibition likely allows pol \u03b7 preferential access to stalled replication forks by delaying Rev1 recruitment. Such an ordered polymerase-recruitment mechanism would reduce the likelihood of mutations.<\/jats:p>","DOI":"10.3390\/biom16081172","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:57:26Z","timestamp":1786521446000},"page":"1172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Oligomeric State of Rad6-Rad18 and Its Interactions with Translesion Synthesis Proteins"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9715-9314","authenticated-orcid":false,"given":"Tyler J.","family":"Woodward","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Iowa, Iowa City, IA 52242-1109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5909-8864","authenticated-orcid":false,"given":"Brittany M.","family":"Ripley","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Iowa, Iowa City, IA 52242-1109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3886-8764","authenticated-orcid":false,"given":"Justin A.","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Iowa, Iowa City, IA 52242-1109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Todd","family":"Washington","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Iowa, Iowa City, IA 52242-1109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","first-page":"771","article-title":"Cell Death Response to DNA Damage","volume":"92","author":"Wang","year":"2019","journal-title":"Yale J. Biol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrc.2015.2","article-title":"DNA damage and the balance between survival and death in cancer biology","volume":"16","author":"Roos","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-012414-040424","article-title":"DNA replication stress as a hallmark of cancer","volume":"10","author":"Macheret","year":"2015","journal-title":"Annu. Rev. 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