2020年6月4日，《细胞》杂志在线发表了美国哥伦比亚大学Eric C. Greene小组的最新成果。他们发现，Rad54在同源重组（HR）过程中驱动ATP水解依赖性的DNA序列比对。

研究人员使用单分子成像来证明了Rad54（一种在所有真核生物中均发现的保守Snf2样蛋白）将同源性搜索从基础HR机器的扩散途径转换为主动过程。在这一主动过程中，DNA序列通过 ATP依赖性分子马达驱动的机制来对齐。

研究人员进一步证明Rad54破坏了供体模板链，使搜索能够在由复制蛋白A（RPA）结合的DNA气泡状结构中进行。这些研究结果表明，Rad54与RPA一起可以从根本上改变HR期间DNA序列的排列方式。

据了解，HR有助于维持基因组完整性，并且HR缺陷会导致疾病，尤其是癌症。在HR期间，必须通过称为同源性搜索的过程将受损的DNA与未损坏的模板对齐。尽管进行了数十年的研究，但此搜索的关键方面仍不确定。

附：英文原文

Title: Rad54 Drives ATP Hydrolysis-Dependent DNA Sequence Alignment during Homologous Recombination

Author: J. Brooks Crickard, Corentin J. Moevus, Youngho Kwon, Patrick Sung, Eric C. Greene

Issue&Volume: 2020-06-04

Abstract: Homologous recombination (HR) helps maintain genome integrity, and HR defects giverise to disease, especially cancer. During HR, damaged DNA must be aligned with anundamaged template through a process referred to as the homology search. Despite decadesof study, key aspects of this search remain undefined. Here, we use single-moleculeimaging to demonstrate that Rad54, a conserved Snf2-like protein found in all eukaryotes,switches the search from the diffusion-based pathways characteristic of the basalHR machinery to an active process in which DNA sequences are aligned via an ATP-dependentmolecular motor-driven mechanism. We further demonstrate that Rad54 disrupts the donortemplate strands, enabling the search to take place within a migrating DNA bubble-likestructure that is bound by replication protein A (RPA). Our results reveal that Rad54,working together with RPA, fundamentally alters how DNA sequences are aligned duringHR.

DOI: 10.1016/j.cell.2020.04.056

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30562-6