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首页> 外文期刊>Current Biology: CB >Redox-Responsive Zinc Finger Fidelity Switch in Homing Endonuclease and Intron Promiscuity in Oxidative Stress
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Redox-Responsive Zinc Finger Fidelity Switch in Homing Endonuclease and Intron Promiscuity in Oxidative Stress

机译：归巢核酸内切酶中氧化还原反应性锌指保真开关和氧化应激中内含子混杂

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It is well understood how mobile introns home to allelic sites, but how they are stimulated to transpose to ectopic locations on an evolutionary timescale is unclear [1]. Here we show that a group I intron can move to degenerate sites under oxidizing conditions. The phage T4 td intron endonuclease, I-TevI, is responsible for this infidelity. We demonstrate that I-TevI, which promotes mobility and is subject to autorepression [2] and translational control [3], is also regulated posttranslationally by a redox mechanism. Redox regulation is exercised by a zinc finger (ZF) in a linker that connects the catalytic domain of I-TevI to the DNA binding domain. Four cysteines coordinate Zn[super]2+ in the ZF, which ensures that I-TevI cleaves its DNA substrate at a fixed distance, 23-25 nucleotides upstream of the intron insertion site [4]. We show that the fidelity of I-TevI cleavage is controlled by redox-responsive Zn[super]2+ cycling. When the ZF is mutated, or after exposure of the wild-type I-TevI to H sub(2O) sub(2), intron homing to degenerate sites is increased, likely because of indiscriminate DNA cleavage. These results suggest a mechanism for rapid intron dispersal, joining recent descriptions of the activation of biomolecular processes by oxidative stress through cysteine chemistry [[5] and [6]]. Highlights: Zn[super]2+ content of I-TevI intron endonuclease is redox sensitive Cleavage fidelity of I-TevI is lost upon ablation of the zinc finger Intron mobility to degenerate sites is increased when zinc finger is dysfunctional Oxidative stress stimulates intron promiscuity
机译：众所周知，移动内含子如何归位于等位基因位点，但是如何在进化的时间尺度上刺激它们转座到异位位置尚不清楚[1]。在这里，我们证明了I组内含子可以在氧化条件下移动至简并位点。噬菌体T4 td内含子核酸内切酶I-TevI​​造成了这种不忠。我们证明，I-TevI​​促进了活动性，并受到自动抑制[2]和翻译控制[3]的影响，还通过氧化还原机制对翻译后进行调节。氧化锌调节是通过锌指（ZF）在连接I-TevI​​的催化结构域与DNA结合结构域的连接子中进行的。四个半胱氨酸在ZF中配位Zn2 +，从而确保I-TevI​​在内含子插入位点上游23-25个核苷酸的固定距离处切割其DNA底物[4]。我们表明，I-TevI​​切割的保真度由氧化还原响应的Zn 2+循环控制。当ZF发生突变时，或在野生型I-TevI​​暴露于H sub（2O）sub（2）后，内含子归巢到简并位点的可能性增加，这可能是因为DNA的切割不加区分。这些结果提示了一种快速内含子扩散的机制，并加入了有关通过半胱氨酸化学氧化应激激活生物分子过程的最新描述[5]和[6]。重点：I-TevI​​内含子内切酶的Zn [2] +含量对氧化还原敏感消融锌指后失去I-TevI​​的切割保真度当锌指功能障碍时，内含子变性部位的迁移率增加氧化应激刺激内含子杂乱

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