Inhibition of DNA ligase activity by arsenite: a possible mechanism of its comutagenesis.
Inhibition of DNA ligase activity by arsenite: a possible mechanism of its comutagenesis.
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发表时间：
1989
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通讯作者：
J. H. Li;T. Rossman
中科院分区：
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作者：
J. H. Li;T. Rossman
我们以前已经表明，MNU诱导的DNA修复的抑制亚砷酸盐发生在中国仓鼠V79细胞的切口步骤后。我们现在报告，核DNA连接酶活性被抑制后，亚砷酸盐处理和抑制的活动主要是DNA连接酶II。DNA连接酶II的组成型和MNU诱导型水平均被抑制。在体外加入亚砷酸盐也表明DNA连接酶II比DNA连接酶I对亚砷酸盐抑制更敏感。由于DNA连接酶II被报道参与切除修复的连接步骤，亚砷酸盐对其的抑制是亚砷酸盐抑制DNA修复的可能机制，并且可以解释亚砷酸盐作为与许多不同类型的诱变剂的共诱变剂的事实。亚砷酸盐的致癌性也可能是连接酶抑制的结果。
We have previously shown that the inhibition of MNU-induced DNA repair by arsenite occurs after the incision step in Chinese hamster V79 cells. We now report that nuclear DNA ligase activity is inhibited after arsenite treatment and that the inhibited activity is mostly DNA ligase II. Both constitutive and MNU-inducible levels of DNA ligase II are inhibited. The addition of arsenite in vitro also indicates that DNA ligase II is more sensitive to arsenite inhibition than DNA ligase I. Since DNA ligase II is reported to be involved in the ligation step of excision repair, its inhibition by arsenite is a likely mechanism for the inhibition of DNA repair by arsenite and may account for the fact that arsenite acts as a comutagen with a number of different types of mutagens. The carcinogenicity of arsenite may also be a result of ligase inhibition.