Rdh54 stabilizes Rad51 at displacement loop intermediates to regulate genetic exchange between chromosomes.
Rdh54 stabilizes Rad51 at displacement loop intermediates to regulate genetic exchange between chromosomes.
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DOI：
10.1371/journal.pgen.1010412
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发表时间：
2022-09
期刊：
影响因子：
4.5
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中科院分区：
文献类型：
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同源重组（HR）是一种双链断裂DNA修复途径，保留染色体结构。为了修复受损的DNA，HR使用位于基因组其他位置的完整供体DNA序列。双链断裂修复后，DNA序列信息可以通过不同的机制在供体和受体DNA分子之间转移，包括同源染色体之间形成的DNA交换。DNA序列转移的调控是有效完成HR和维持基因组完整性的重要步骤。例如，同源染色体之间的有丝分裂信息交换可导致杂合性丢失（洛），并且在高等真核生物中，可导致癌症的发展。Rdh 54是一种高度保守的DNA转位酶，在HR过程中发挥重要作用，在rdh 54 Δ菌株中存在的几种表型表明Rdh 54可能在HR过程中调节DNA的有效交换。我们的数据表明，RDH 54调节DNA链交换的稳定Rad 51在早期的HR中间称为位移环（D-loop）。Rdh 54的作用与DNA马达蛋白Rad 54去除Rad 51相反。此外，我们发现，Rdh 54的催化突变等位基因，rdh 54 K318 R的表达，有利于非交叉结果。从这些结果中，我们提出了一个模型，如何Rdh 54可能在同源重组过程中动力学调节链交换。同源重组是DNA双链断裂修复的重要途径。就本研究而言，人力资源可分为两个阶段。第一个阶段是DNA修复阶段，其中断裂的DNA分子被固定。在第二阶段，信息可以从一个DNA分子转移到另一个。酶利用ATP水解的力量来移动沿着dsDNA的援助，在调节这两个阶段的HR. In这项工作中，我们专注于未充分研究的DNA马达蛋白Rdh 54。我们结合遗传和生物化学方法表明，Rdh 54调节HR通过稳定重组酶蛋白Rad 51在早期HR中间体。
Homologous recombination (HR) is a double-strand break DNA repair pathway that preserves chromosome structure. To repair damaged DNA, HR uses an intact donor DNA sequence located elsewhere in the genome. After the double-strand break is repaired, DNA sequence information can be transferred between donor and recipient DNA molecules through different mechanisms, including DNA crossovers that form between homologous chromosomes. Regulation of DNA sequence transfer is an important step in effectively completing HR and maintaining genome integrity. For example, mitotic exchange of information between homologous chromosomes can result in loss-of-heterozygosity (LOH), and in higher eukaryotes, the development of cancer. The DNA motor protein Rdh54 is a highly conserved DNA translocase that functions during HR. Several existing phenotypes in rdh54Δ strains suggest that Rdh54 may regulate effective exchange of DNA during HR. In our current study, we used a combination of biochemical and genetic techniques to dissect the role of Rdh54 on the exchange of genetic information during DNA repair. Our data indicate that RDH54 regulates DNA strand exchange by stabilizing Rad51 at an early HR intermediate called the displacement loop (D-loop). Rdh54 acts in opposition to Rad51 removal by the DNA motor protein Rad54. Furthermore, we find that expression of a catalytically inactivate allele of Rdh54, rdh54K318R, favors non-crossover outcomes. From these results, we propose a model for how Rdh54 may kinetically regulate strand exchange during homologous recombination. Homologous recombination is an important pathway in repairing DNA double strand breaks. For the purposes of this study, HR can be divided into two stages. The first is a DNA repair stage in which the broken DNA molecule is fixed. In the second stage, information can move from one DNA molecule to another. Enzymes that use the power of ATP hydrolysis to move along dsDNA aid in regulating both stages of HR. In this work we focused on the understudied DNA motor protein Rdh54. We combined genetic and biochemical approaches to show that Rdh54 regulates HR by stabilizing the recombinase protein Rad51 at early HR intermediates.
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