Analysis of nucleotide insertion opposite 2,2,4-triamino-5(2H)-oxazolone by eukaryotic B- and Y-family DNA polymerases
| Autor: | Taishu Kawada, Masayuki Morikawa, Katsuhito Kino, Hiroshi Miyazawa, Takanobu Kobayashi, Masayo Suzuki |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
chemistry.chemical_classification
biology DNA polymerase Guanine Nucleotides General Medicine DNA-Directed DNA Polymerase Toxicology Molecular biology Guanidines Oxazolone chemistry.chemical_compound chemistry biology.protein REV1 heterocyclic compounds Nucleotide Primer (molecular biology) Gene Polymerase |
| Zdroj: | Chemical research in toxicology. 28(6) |
| ISSN: | 1520-5010 |
| Popis: | Mutations induced by oxidative DNA damage can cause diseases such as cancer. In particular, G:C-T:A and G:C-C:G transversions are caused by oxidized guanine and have been observed in the p53 and K-ras genes. We focused on an oxidized form of guanine, 2,2,4-triamino-5(2H)-oxazolone (Oz), as a cause of G:C-C:G transversions based on our earlier elucidation that DNA polymerases (Pols) α, β, γ, ε, η, I, and IV incorporate dGTP opposite Oz. The nucleotide insertion and extension of Pols δ, ζ, ι, κ, and REV1, belonging to the B- and Y-families of DNA polymerases, were analyzed for the first time. Pol δ incorporated dGTP, in common with other replicative DNA polymerases. Pol ζ incorporated dGTP and dATP, and the efficiency of elongation up to full-length beyond Oz was almost the same as that beyond G. Although nucleotide incorporation by Pols ι or κ was also error-prone, they did not extend the primer. On the other hand, the polymerase REV1 predominantly incorporated dCTP opposite Oz more efficiently than opposite 8-oxo-7,8-dihydroguanine, guanidinohydantoin, or tetrahydrofuran. Here, we demonstrate that Pol ζ can efficiently replicate DNA containing Oz and that REV1 can prevent G:C-C:G transversions caused by Oz. |
| Databáze: | OpenAIRE |
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