DNA Polymerase κによるDNA損傷のバイパスと突然変異の誘発(第13回公開シンポジウム「環境変異原と遺伝子不安定性」)

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We have identified Pol κ as a mammalian homologue of the Escherichia coli DinB protein (=DNA polymerase IV). We overproduced and purified a truncated form of Pol κ lacking the C-terminal 310 amino acids, which exhibited a very similar enzymatic activity with the intact form (870 amino acids). Pol κ 15 unable to bypass UV-induced T-T cyclobutane pyrimidine dimer or (6-4) photoproduct, but it can bypass benzo [a] pyrene (B [a]P) -adducted guanine efficiently and accurately. We isolated mutants defective for the Pol κ function from a mouse embryonic stem cell line. The Pol κ -defective mutant cells are highly sensitive both to killing and mutagenesis induced by B [a] P. The spectrum of B [a] P-induced mutations in the Pol κ -defective mutant cells is different from that in the wild-type cells, which suggested that Pol η might be involved in error-prone bypass of B [a] P-adducted guanines in the absence of Pol κ. Thus, our results provide strong evidence that Pol κ plays a crucial role in protecting cells from the genotoxic effects of B [a] P, and by implication of other polyaromatic hydrocarbons.
日本環境変異原学会の論文
2002-11-13