7,8-Dihydro-8-oxo-1,N6-ethenoadenine: an exclusively Hoogsteen-paired thymine mimic in DNA that induces A→T transversions in Escherichia coli
| العنوان: | 7,8-Dihydro-8-oxo-1,N6-ethenoadenine: an exclusively Hoogsteen-paired thymine mimic in DNA that induces A→T transversions in Escherichia coli |
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| المؤلفون: | Andrey V Aralov, Nina Gubina, Cristina Cabrero, Vladimir B Tsvetkov, Anton V Turaev, Bogdan I Fedeles, Robert G Croy, Ekaterina A Isaakova, Denis Melnik, Svetlana Dukova, Dmitriy Y Ryazantsev, Alexei A Khrulev, Anna M Varizhuk, Carlos González, Timofei S Zatsepin, John M Essigmann |
| المساهمون: | Massachusetts Institute of Technology, National Institutes of Health (US), Ministerio de Ciencia e Innovación (España), Ministry of Science and Higher Education of the Russian Federation |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | Oxford University Press, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | DNA Repair, Genetics, Escherichia coli, DNA, Base Pairing, Thymine |
| الوصف: | 14 pags., 9 figs. This work investigated the structural and biological properties of DNA containing 7,8-dihydro-8-oxo-1,N6-ethenoadenine (oxo-ϵA), a non-natural synthetic base that combines structural features of two naturally occurring DNA lesions (7,8-dihydro-8-oxoadenine and 1,N6-ethenoadenine). UV-, CD-, NMR spectroscopies and molecular modeling of DNA duplexes revealed that oxo-ϵA adopts the non-canonical syn conformation (χ = 65º) and fits very well among surrounding residues without inducing major distortions in local helical architecture. The adduct remarkably mimics the natural base thymine. When considered as an adenine-derived DNA lesion, oxo-ϵA was >99% mutagenic in living cells, causing predominantly A→T transversion mutations in Escherichia coli. The adduct in a single-stranded vector was not repaired by base excision repair enzymes (MutM and MutY glycosylases) or the AlkB dioxygenase and did not detectably affect the efficacy of DNA replication in vivo. When the biological and structural data are viewed together, it is likely that the nearly exclusive syn conformation and thymine mimicry of oxo-ϵA defines the selectivity of base pairing in vitro and in vivo, resulting in lesion pairing with A during replication. The base pairing properties of oxo-ϵA, its strong fluorescence and its invisibility to enzymatic repair systems in vivo are features that are sought in novel DNA-based probes and modulators of gene expression. MIT Skoltech Next Generation Program Pilot Grant (to J.M.E.); National Institutes of Health (NIH) [R01-CA080024 to J.M.E.]; NIEHS Center Grant [P30-ES002109 (to Center for Environmental Health Sciences, which provided access to NGS facilities)]; Skoltech (to T.S.Z.); MICINN [PID2020-116620GB-I00 to C.G.]; Ministry of Science and Higher Education Russian Federation [07515-2021-1049 to A.V.A. – synthesis and UV/CD studies]. Funding for open access charge: Skoltech. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c9a0e96021c16b9d7b61161c12d1e47Test http://hdl.handle.net/10261/268285Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2c9a0e96021c16b9d7b61161c12d1e47 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |