Lee Y H, Fang S C, Wei R D
Toxicology. 1984 Oct;33(1):43-57. doi: 10.1016/0300-483x(84)90015-5.
PR toxin, a mycotoxin from cultures of Penicillium roqueforti, inhibited the in vitro activities of rat liver DNA polymerase alpha, beta, and gamma irrespectively of the nature of template-primer used. The concentration required for 50% inhibition of DNA polymerase alpha was 5-6 X 10(-6) M, while those for DNA polymerase beta and gamma were several times higher. By using DNA polymerase beta as a model, and based on the enzyme and template-primer concentration effects and also from the kinetic analysis on PR toxin inhibition, we concluded that two action mechanisms of PR toxin inhibition on in vitro DNA synthesis are operative. Inhibition of the in vitro DNA synthesis directed by DNA template was mediated primarily through alteration of the enzyme itself, whereas in the DNA synthesis reaction directed by RNA template DNA primer, the impairment of template or primer function due to PR toxin treatment probably had occurred. The inhibition of DNA polymerase by PR toxin persisted even after exhaustive dialysis. Addition of PR toxin to an ongoing reaction also inhibited DNA synthesis. Inactivation of DNA polymerase activity of PR toxin likely involved some essential amino acid residues other than sulfhydryl groups.
PR毒素是一种来自罗克福青霉培养物的霉菌毒素，它能抑制大鼠肝脏DNA聚合酶α、β和γ的体外活性，且与所用模板引物的性质无关。抑制DNA聚合酶α活性50%所需的浓度为5-6×10⁻⁶M，而抑制DNA聚合酶β和γ活性所需的浓度则高出数倍。以DNA聚合酶β为模型，基于酶和模板引物浓度效应以及对PR毒素抑制的动力学分析，我们得出结论，PR毒素抑制体外DNA合成有两种作用机制。由DNA模板指导的体外DNA合成抑制主要是通过酶本身的改变介导的，而在由RNA模板DNA引物指导的DNA合成反应中，PR毒素处理可能导致模板或引物功能受损。即使经过彻底透析，PR毒素对DNA聚合酶的抑制作用仍然存在。向正在进行的反应中添加PR毒素也会抑制DNA合成。PR毒素使DNA聚合酶活性失活可能涉及除巯基以外的一些必需氨基酸残基。
