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首页> 外文期刊>Molecular cell >Rad54 Functions as a Heteroduplex DNA Pump Modulated by Its DNA Substrates and Rad51 during D Loop Formation
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Rad54 Functions as a Heteroduplex DNA Pump Modulated by Its DNA Substrates and Rad51 during D Loop Formation

机译：Rad54在D环形成过程中充当由其DNA底物和Rad51调控的异源双链DNA泵

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摘要

The displacement loop (D loop) is the product of homology search and DNA strand invasion, constituting a central intermediate in homologous recombination (HR). In eukaryotes, the Rad51 DNA strand exchange protein is assisted in D loop formation by the Rad54 motor protein. Curiously, Rad54 also disrupts D loops. How these opposing activities are coordinated toward productive recombination is unknown. Moreover, a seemingly disparate function of Rad54 is removal of Rad51 from heteroduplex DNA (hDNA) to allow HR-associated DNA synthesis. Here, we uncover features of D loop formation/dissociation dynamics, employing Rad51 filaments formed on ssDNAs that mimic the physiological length and structure of invivo substrates. The Rad54 motor is activated by Rad51 bound to synapsed DNAs and guided by a ssDNA-binding domain. We present a unified model wherein Rad54 acts as an hDNA pump that drives D loop formation while simultaneously removing Rad51 from hDNA, consolidating both ATP-dependent activities of Rad54 into a single mechanistic step.
机译：置换环（D环）是同源搜索和DNA链入侵的产物，构成同源重组（HR）的中心中间体。在真核生物中，Rad54运动蛋白辅助Rad51 DNA链交换蛋白形成D环。奇怪的是，Rad54还破坏了D循环。这些相反的活动如何协调进行有效的重组尚不清楚。而且，Rad54的一个貌似完全不同的功能是从异源双链DNA（hDNA）中去除Rad51，从而允许HR相关的DNA合成。在这里，我们揭示了D环形成/解离动力学的特征，它采用了在ssDNA上形成的Rad51细丝来模仿体内底物的生理长度和结构。 Rad54马达由结合到突触DNA的Rad51激活，并由ssDNA结合域引导。我们提出了一个统一的模型，其中Rad54充当hDNA泵，驱动D环形成，同时从hDNA中删除Rad51，将Rad54的两个ATP依赖性活动整合为一个机械步骤。

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