000002154 001__ 2154 000002154 005__ 20260429175304.0 000002154 0247_ $$2DOI$$a10.6083/M4H993F2 000002154 037__ $$aETD 000002154 245__ $$aMutagenic consequences of replication bypass of N3 uracil and N[superscript 2] guanine DNA adducts 000002154 260__ $$bOregon Health and Science University 000002154 269__ $$a2006 000002154 336__ $$aDissertation 000002154 502__ $$bPh.D. 000002154 502__ $$gMolecular Microbiology & Immunology (sunsetting) 000002154 520__ $$aDNA is continuously exposed to endogenous and exogenous agents that form DNA adducts, which can promote mutagenesis and carcinogenesis. This dissertation examined the mutagenicity and replication bypass of site‑specifically introduced DNA adducts derived from butadiene, vinyl chloride, 4‑hydroxynonenal, and crotonaldehyde. Using mammalian single‑stranded shuttle vectors, these lesions were shown to induce error‑prone replication with lesion‑specific mutation frequencies. Butadiene‑derived N3‑deoxyuridine adducts were the most mutagenic and required translesional synthesis by polymerases η and ζ for efficient bypass. Collectively, these findings elucidate mechanisms by which structurally distinct DNA adducts contribute to mutagenesis in mammalian cells. 000002154 540__ $$fCC BY 000002154 542__ $$fIn copyright - single owner 000002154 650__ $$aButadienes$$015921 000002154 650__ $$aAldehydes$$014422 000002154 650__ $$aMutagenesis$$029042 000002154 650__ $$aVinyl Chloride$$027824 000002154 650__ $$aDNA Replication$$017991 000002154 650__ $$aDNA Adducts$$031053 000002154 650__ $$aDNA-Directed DNA Polymerase$$017989 000002154 691__ $$aSchool of Medicine$$041369 000002154 692__ $$aDepartment of Molecular Microbiology and Immunology$$041429 000002154 7001_ $$aFernandes, Priscilla$$uOregon Health and Science University$$041354 000002154 7201_ $$aLloyd, Stephen$$uOregon Health and Science University$$041354$$7Personal$$eMentor 000002154 8564_ $$97dd23df1-757c-42ab-9d49-86b47a81c690$$s5136096$$uhttps://digitalcollections.ohsu.edu/record/2154/files/2883_etd.pdf$$ePublic$$2e7ff74de84b2d2b8feed25c13c65452a$$31 000002154 901__ $$a<p>These documents are archival records. They are retained for historical reference only. </p><p><b>Need an accessible version? Use the ‘Get Accessible Copy’ link above.</b></p> 000002154 905__ $$a/rest/prod/hh/63/sw/10/hh63sw105 000002154 909CO $$ooai:digitalcollections.ohsu.edu:2154$$pstudent-work 000002154 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument 000002154 980__ $$aTheses and Dissertations