Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase
7,8-Dihydro-8-oxoguanine (oxoG) is the most abundant oxidative DNA lesion with dual coding properties. It forms both Watson−Crick (<i>anti</i>)oxoG:(<i>anti</i>)C and Hoogsteen (<i>syn</i>)oxoG:(<i>anti</i>)A base pairs without a significant...
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MDPI AG
2019-05-01
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| Series: | Crystals |
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| Online Access: | https://www.mdpi.com/2073-4352/9/5/269 |
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| author | Anna V. Yudkina Evgeniy S. Shilkin Anton V. Endutkin Alena V. Makarova Dmitry O. Zharkov |
| author_facet | Anna V. Yudkina Evgeniy S. Shilkin Anton V. Endutkin Alena V. Makarova Dmitry O. Zharkov |
| author_sort | Anna V. Yudkina |
| collection | DOAJ |
| description | 7,8-Dihydro-8-oxoguanine (oxoG) is the most abundant oxidative DNA lesion with dual coding properties. It forms both Watson−Crick (<i>anti</i>)oxoG:(<i>anti</i>)C and Hoogsteen (<i>syn</i>)oxoG:(<i>anti</i>)A base pairs without a significant distortion of a B-DNA helix. DNA polymerases bypass oxoG but the accuracy of nucleotide incorporation opposite the lesion varies depending on the polymerase-specific interactions with the templating oxoG and incoming nucleotides. High-fidelity replicative DNA polymerases read oxoG as a cognate base for A while treating oxoG:C as a mismatch. The mutagenic effects of oxoG in the cell are alleviated by specific systems for DNA repair and nucleotide pool sanitization, preventing mutagenesis from both direct DNA oxidation and oxodGMP incorporation. DNA translesion synthesis could provide an additional protective mechanism against oxoG mutagenesis in cells. Several human DNA polymerases of the X- and Y-families efficiently and accurately incorporate nucleotides opposite oxoG. In this review, we address the mutagenic potential of oxoG in cells and discuss the structural basis for oxoG bypass by different DNA polymerases and the mechanisms of the recognition of oxoG by DNA glycosylases and dNTP hydrolases. |
| first_indexed | 2024-04-13T08:46:46Z |
| format | Article |
| id | doaj.art-9356438cb2e4463185ac4611b6251330 |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-04-13T08:46:46Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj.art-9356438cb2e4463185ac4611b62513302022-12-22T02:53:39ZengMDPI AGCrystals2073-43522019-05-019526910.3390/cryst9050269cryst9050269Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous NucleobaseAnna V. Yudkina0Evgeniy S. Shilkin1Anton V. Endutkin2Alena V. Makarova3Dmitry O. Zharkov4Novosibirsk State University, 1 Pirogova St., 630090 Novosibirsk, RussiaRAS Institute of Molecular Genetics, 2 Kurchatova Sq., 123182 Moscow, RussiaNovosibirsk State University, 1 Pirogova St., 630090 Novosibirsk, RussiaRAS Institute of Molecular Genetics, 2 Kurchatova Sq., 123182 Moscow, RussiaNovosibirsk State University, 1 Pirogova St., 630090 Novosibirsk, Russia7,8-Dihydro-8-oxoguanine (oxoG) is the most abundant oxidative DNA lesion with dual coding properties. It forms both Watson−Crick (<i>anti</i>)oxoG:(<i>anti</i>)C and Hoogsteen (<i>syn</i>)oxoG:(<i>anti</i>)A base pairs without a significant distortion of a B-DNA helix. DNA polymerases bypass oxoG but the accuracy of nucleotide incorporation opposite the lesion varies depending on the polymerase-specific interactions with the templating oxoG and incoming nucleotides. High-fidelity replicative DNA polymerases read oxoG as a cognate base for A while treating oxoG:C as a mismatch. The mutagenic effects of oxoG in the cell are alleviated by specific systems for DNA repair and nucleotide pool sanitization, preventing mutagenesis from both direct DNA oxidation and oxodGMP incorporation. DNA translesion synthesis could provide an additional protective mechanism against oxoG mutagenesis in cells. Several human DNA polymerases of the X- and Y-families efficiently and accurately incorporate nucleotides opposite oxoG. In this review, we address the mutagenic potential of oxoG in cells and discuss the structural basis for oxoG bypass by different DNA polymerases and the mechanisms of the recognition of oxoG by DNA glycosylases and dNTP hydrolases.https://www.mdpi.com/2073-4352/9/5/2697,8-Dihydro-8-oxoguaninemutagenesisDNA polymerasesbase excision repairDNA glycosylasesnucleotide hydrolasestranslesion DNA synthesis |
| spellingShingle | Anna V. Yudkina Evgeniy S. Shilkin Anton V. Endutkin Alena V. Makarova Dmitry O. Zharkov Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase Crystals 7,8-Dihydro-8-oxoguanine mutagenesis DNA polymerases base excision repair DNA glycosylases nucleotide hydrolases translesion DNA synthesis |
| title | Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase |
| title_full | Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase |
| title_fullStr | Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase |
| title_full_unstemmed | Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase |
| title_short | Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase |
| title_sort | reading and misreading 8 oxoguanine a paradigmatic ambiguous nucleobase |
| topic | 7,8-Dihydro-8-oxoguanine mutagenesis DNA polymerases base excision repair DNA glycosylases nucleotide hydrolases translesion DNA synthesis |
| url | https://www.mdpi.com/2073-4352/9/5/269 |
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