Mechanistic Insight Into Cadmium- and Zinc-Induced Inactivation of the Candida albicans Pif1 Helicase.
Mechanistic Insight Into Cadmium- and Zinc-Induced Inactivation of the Candida albicans Pif1 Helicase.
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镉和锌诱导白色念珠菌 Pif1 解旋酶失活的机制研究
DOI：
10.3389/fmolb.2021.778647
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发表时间：
2021
影响因子：
5
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Zhang B;Zhang Q;Zhu X;Li D;Duan X;Jin J;Wang K;Xie Y;Liu Y
锌和镉是环境污染物，可通过影响DNA修复蛋白的活性而引起疾病。在这项研究中，我们研究了Zn 2+和Cd 2+对白色念珠菌Pif 1的影响，Pif 1是一种DNA修复解旋酶，在确保基因组稳定性方面起着关键作用。结果表明，Zn ~（2+）和Cd ~（2+）对CaPif 1的ATP酶活性和解旋活性均有强烈的抑制作用，但对CaPif 1的DNA结合活性没有影响。高浓度的Cd ~（2+）可与CaPif 1的半胱氨酸残基结合，其抑制作用似乎难以被乙二胺四乙酸恢复，而Zn ~（2+）的抑制作用则可以。当两种离子均处于低浓度时，增加反应中ATP的浓度可适当减弱Zn 2+的抑制作用，而半胱氨酸则可降低Cd 2+的抑制作用。此外，我们发现，对于Cd 2+和Zn 2+的抑制作用是近100倍，在还原环境中比在非还原环境。当重金属刺激人体反应时，人体环境的还原性减弱，从而CaPif 1对重金属的耐受性会更强。我们认为CaPif 1可能通过这种机制抵抗重金属的毒性。总而言之，我们的研究结果为重金属对DNA修复蛋白的毒性机制提供了新的见解。
Zinc and cadmium are environmental contaminants that can cause disease by affecting the activity of DNA-repair proteins. In this study, we investigated the effect of Zn2+ and Cd2+ on the Candida albicans Pif1, a DNA-repair helicase that plays a critical role in ensuring genomic stability. We show that Zn2+ and Cd2+ strongly inhibit both the ATPase and the unwinding activities of CaPif1, but have no effect on its DNA binding activity. High concentrations of Cd2+ may bind to the cysteine residues of CaPif1, and its inhibition appears to be difficult to be restored by ethylene diamine tetraacetic acid, while inhibition due to Zn2+ can. When the two ions are at low concentrations, increasing the concentration of ATP in the reaction can appropriately weaken the inhibitory effect of Zn2+, while cysteine can reduce the inhibitory effect of Cd2+. In addition, we found that for both Cd2+ and Zn2+ the inhibition effects were nearly 100 times greater in reduced environments than in non-reducing environments. When heavy metals stimulate the body’s response, the environment of the body becomes less reducing, and thus the tolerance of CaPif1 to heavy metals will be stronger. We propose that CaPif1 may resist the toxicity of heavy metals through this mechanism. Altogether, our results provide new insights into the mechanisms by which heavy metals are toxic to DNA-repair proteins.
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影响因子：
64.8
作者：
Boulé, JB;Vega, LR;Zakian, VA
通讯作者：
Zakian, VA
G-四链体和富含 G 的序列通过减少 ss/dsDNA 连接处的等待时间来刺激 Pif1p 催化的下游双链体 DNA 解旋
影响因子：
14.9
作者：
Zhang B;Wu WQ;Liu NN;Duan XL;Li M;Dou SX;Hou XM;Xi XG
通讯作者：
Xi XG
影响因子：
3.5
作者：
Witkiewicz-Kucharczyk, A;Bal, W
通讯作者：
Bal, W
影响因子：
2
作者：
Futami, Kazunobu;Shimamoto, Akira;Furuichi, Yasuhiro
通讯作者：
Furuichi, Yasuhiro
影响因子：
5.6
作者：
Frick, David N.;Banik, Sukalyani;Rypma, Ryan S.
通讯作者：
Rypma, Ryan S.