Analysis of Nucleotide Insertion Opposite 2,2,4-Triamino-5(2H)-oxazolone by Eukaryotic B- and Y-Family DNA Polymerases

作者：Suzuki Masayo; Kino Katsuhito^*; Kawada Taishu; Morikawa Masayuki; Kobayashi Takanobu; Miyazawa Hiroshi

来源：Chemical Research in Toxicology, 2015, 28(6): 1307-1316.

DOI：10.1021/acs.chemrestox.5b00114

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) alpha, beta, gamma, epsilon, eta, I, and IV incorporate dGTP opposite Oz. The nucleotide insertion and extension of Pols delta, zeta, iota, kappa, and REV1, belonging to the B- and Y-families of DNA polymerases, were analyzed for the first time. Pol delta incorporated dGTP, in common with other replicative DNA polymerases. Pol delta 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 iota or kappa 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 zeta can efficiently replicate DNA containing Oz and that REV1 can prevent G:C-C:G transversions caused by Oz.

• 出版日期2015-6