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Copper Inhibits the AlkB Family DNA Repair Enzymes under Wilson’s Disease Condition
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2017-09-26 00:00:00 , DOI: 10.1021/acs.chemrestox.7b00230
Ke Bian 1 , Fangyi Chen 1 , Zachary T. Humulock 1 , Qi Tang 1 , Deyu Li 1
Affiliation  

Disturbed metabolism of copper ions can cause diseases such as Wilson’s disease (WD). In this work, we investigated the inhibitory effect of Cu(II) ion in vitro on the AlkB family DNA repair enzymes, which are members of the Fe(II)/alpha-ketoglutarate-dependent dioxygenase and include human ALKBH2, ALKBH3, and E. coli AlkB proteins. None of the three proteins was significantly inhibited under normal cellular copper concentrations. However, under WD related condition, we observed that the activities of all three enzymes were strongly suppressed (from 95.2 to 100.0%). We also noted the repair efficiency under ds-DNA condition was less susceptible than ss-DNA to the inhibition.

中文翻译:

铜在威尔逊病条件下抑制AlkB家族DNA修复酶

铜离子代谢紊乱会导致疾病,例如威尔逊氏病(WD)。在这项工作中,我们研究了Cu(II)离子在体外对AlkB家族DNA修复酶的抑制作用,该酶是Fe(II)/α-酮戊二酸依赖性双加氧酶的成员,包括人ALKBH2,ALKBH3和E大肠杆菌AlkB蛋白。在正常细胞铜浓度下,这三种蛋白质均未受到明显抑制。但是,在WD相关条件下,我们观察到所有三种酶的活性均被强烈抑制(从95.2%降至100.0%)。我们还注意到在ds-DNA条件下的修复效率不如ss-DNA容易受到抑制。
更新日期:2017-09-26
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