Conservation of the insert-2 motif confers Rev1 from different species with an ability to disrupt G-quadruplexes and stimulate translesion DNA synthesis.
Conservation of the insert-2 motif confers Rev1 from different species with an ability to disrupt G-quadruplexes and stimulate translesion DNA synthesis.
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DOI：
10.1039/d3cb00027c
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发表时间：
2023-07-05
影响因子：
4.1
通讯作者：
中科院分区：
文献类型：
--
作者：
在某些生物中，G-四链体（G4）结构的复制由Rev 1 DNA聚合酶支持。我们以前表明，在人Rev 1（hRev 1）的插入-2基序的残基增加了G4 DNA的酶的亲和力和介导的抑制突变复制G4基序附近。我们现在已经研究了G4-选择性的性质，从其他物种的Rev 1的保护。我们比较了来自斑马鱼（zRev 1）、酿酒酵母（yRev 1）和杜氏利什曼原虫（lRev 1）的Rev 1与hRev 1，包括hRev 1的插入-2突变形式（E466 A/Y 470 A或EY）。我们发现zRev 1保留了人类酶的所有G4选择能力，但对EY hRev 1突变体和两种缺乏插入片段-2的Rev 1蛋白（yRev 1和lRev 1）的G4结合亲和力明显减弱。也许最引人注目的是，我们发现插入-2对于G4结构的破坏和DNA聚合酶kappa（pol κ）跨富含鸟嘌呤基序的进行性DNA合成的最佳刺激是重要的。我们的研究结果对Rev 1如何在跨越进化树的不同物种中促进G4复制产生了影响-这表明选择具有强大G4选择性的酶的重要性，这些酶在生物体中具有强大的G4选择性，这些非B DNA结构可以实现特定的生理功能。Rev 1 DNA聚合酶的G-四链体（G4）选择性特性在物种间不同。
In some organisms, the replication of G-quadruplex (G4) structures is supported by the Rev1 DNA polymerase. We previously showed that residues in the insert-2 motif of human Rev1 (hRev1) increased the affinity of the enzyme for G4 DNA and mediated suppression of mutagenic replication near G4 motifs. We have now investigated the conservation of G4-selective properties in Rev1 from other species. We compared Rev1 from Danio rerio (zRev1), Saccharomyces cerevisiae (yRev1), and Leishmania donovani (lRev1) with hRev1, including an insert-2 mutant form of hRev1 (E466A/Y470A or EY). We found that zRev1 retained all of the G4-selective prowess of the human enzyme, but there was a marked attenuation of G4 binding affinity for the EY hRev1 mutant and the two Rev1 proteins lacking insert-2 (yRev1 and lRev1). Perhaps most strikingly, we found that insert-2 was important for disruption of the G4 structure and optimal stimulation of processive DNA synthesis across the guanine-rich motif by DNA polymerase kappa (pol κ). Our findings have implications for how Rev1 might contribute to G4 replication in different species spanning the evolutionary tree – signaling the importance of selection for enzymes with robust G4-selective properties in organisms where these non-B DNA structures may fulfill taxa-specific physiological functions. The G-quadruplex (G4) selective properties of the Rev1 DNA polymerase differ across species.
影响因子：
4.5
作者：
Tellier-Lebegue C;Dizet E;Ma E;Veaute X;Coïc E;Charbonnier JB;Maloisel L
通讯作者：
Maloisel L