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首页> 外文期刊>Nucleic Acids Research >Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage.
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Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage.

机译:PCNA依赖性刺激人类Ape2的3'-磷酸二酯酶和3'-5'核酸外切酶活性在氧化DNA损伤修复中的作用。

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摘要

Human Ape2 protein has 3' phosphodiesterase activity for processing 3'-damaged DNA termini, 3'-5' exonuclease activity that supports removal of mismatched nucleotides from the 3'-end of DNA, and a somewhat weak AP-endonuclease activity. However, very little is known about the role of Ape2 in DNA repair processes. Here, we examine the effect of interaction of Ape2 with proliferating cell nuclear antigen (PCNA) on its enzymatic activities and on targeting Ape2 to oxidative DNA lesions. We show that PCNA strongly stimulates the 3'-5' exonuclease and 3' phosphodiesterase activities of Ape2, but has no effect on its AP-endonuclease activity. Moreover, we find that upon hydrogen-peroxide treatment Ape2 redistributes to nuclear foci where it colocalizes with PCNA. In concert with these results, we provide biochemical evidence that Ape2 can reduce the mutagenic consequences of attack by reactive oxygen species not only by repairing 3'-damaged termini but also by removing 3'-end adenine opposite from 8-oxoG. Based on these findings we suggest the involvement of Ape2 in repair of oxidative DNA damage and PCNA-dependent repair synthesis.
机译:人Ape2蛋白具有3'磷酸二酯酶活性,可处理3'受损的DNA末端,3'-5'核酸外切酶活性可支持从DNA的3'末端去除错配的核苷酸,而AP核酸内切酶活性则较弱。但是,人们对Ape2在DNA修复过程中的作用了解甚少。在这里,我们检查了Ape2与增殖细胞核抗原(PCNA)的相互作用对其酶活性的影响以及对Ape2靶向氧化性DNA损伤的影响。我们显示PCNA强烈刺激Ape2的3'-5'核酸外切酶和3'磷酸二酯酶活性,但对其AP核酸内切酶活性没有影响。此外,我们发现在过氧化氢处理下,Ape2重新分布到与PCNA共定位的核灶。与这些结果相一致,我们提供了生化证据,表明Ape2不仅可以通过修复3'末端受损的末端,而且可以通过去除与8-oxoG相反的3'末端腺嘌呤来减少活性氧攻击的诱变后果。根据这些发现,我们建议Ape2参与氧化DNA损伤的修复和PCNA依赖的修复合成。

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