The catalytic mechanism, metal dependence, substrate specificity, and biodiversity of ribonuclease H.

The catalytic mechanism, metal dependence, substrate specificity, and biodiversity of ribonuclease H.
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DOI:
10.3389/fmicb.2022.1034811
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发表时间:
2022
影响因子:
5.2
通讯作者:
Lu, Zheng
Lu, Zheng
中科院分区:
生物学2区
文献类型:
--
作者:
Pang, Jing;Guo, Qinyu;Lu, Zheng

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单磷酸核糖核苷不可避免地被错误地掺入细胞内的DNA基因组中,它们需要被切除以避免染色体不稳定。核糖核酸酶H(RNases H)是特异性水解RNA/DNA杂交体的RNA链或来自含有一段RNA的DNA的RNA部分的酶,因此它们是DNA完整性所必需的。大量的研究已经对RNase H的催化机制有了一个清晰的认识,但有些问题仍然缺乏明确的答案。本文综述了RNase H催化的三种替代模型。双金属模型是普遍的,但三金属模型表明在催化中涉及第三种阳离子。显然,金属依赖性水解的机制比最初想象的更复杂。我们还讨论了RNase H的金属选择,并分析了化学上相似的阳离子如何发挥不同的功能。底物和裂解位点的特异性不同的RNase H,这是详细解释。一个有趣的现象是,生物体具有不同的RNase H组合,这可能为rnh基因在进化过程中如何转移提供重要线索。是否核糖核酸酶H是必不可少的细胞生长,在体内功能的研究中的一个关键问题,也进行了讨论。这篇文章可能有助于理解RNase H的机制,并开发其潜在的有前途的应用。
Ribonucleoside monophosphates are inevitably misincorporated into the DNA genome inside cells, and they need to be excised to avoid chromosome instability. Ribonucleases H (RNases H) are enzymes that specifically hydrolyze the RNA strand of RNA/DNA hybrids or the RNA moiety from DNA containing a stretch of RNA, they therefore are required for DNA integrity. Extensive studies have drawn a mostly clear picture of the mechanisms of RNase H catalysis, but some questions are still lacking definitive answers. This review summarizes three alternative models of RNase H catalysis. The two-metal model is prevalent, but a three-metal model suggests the involvement of a third cation in catalysis. Apparently, the mechanisms underlying metal-dependent hydrolyzation are more complicated than initially thought. We also discuss the metal choices of RNases H and analyze how chemically similar cations function differently. Substrate and cleavage-site specificities vary among RNases H, and this is explicated in detail. An intriguing phenomenon is that organisms have diverse RNase H combinations, which may provide important hints to how rnh genes were transferred during evolution. Whether RNase H is essential for cellular growth, a key question in the study of in vivo functions, is also discussed. This article may aid in understanding the mechanisms underlying RNase H and in developing potentially promising applications of it.
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