Presynaptic filament dynamics in homologous recombination and DNA repair.
Presynaptic filament dynamics in homologous recombination and DNA repair.
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DOI：
10.3109/10409238.2011.576007
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发表时间：
2011-06
影响因子：
6.5
通讯作者：
Morrical SW
中科院分区：
文献类型：
--
作者：
Liu J;Ehmsen KT;Heyer WD;Morrical SW
同源重组（HR）是一种重要的基因组稳定机制，用于高保真修复DNA双链断裂和恢复停滞或塌陷的DNA复制叉。关键的同源性搜索和DNA链交换步骤的HR是由突触前的催化剂结合到单链DNA的重组酶的螺旋丝。突触前纤维是一种基本的动态结构，其组装、催化转换和拆卸必须与DNA重组、修复和复制机制的其他元件密切协调，以使基因组维持功能有效。在这里，我们回顾了控制突触前纤维的组装，活动和拆卸的主要动态元素：一些内在的，如重组酶ATP结合和水解活性，其他外在的，如ssDNA结合蛋白，介体蛋白和DNA马达蛋白。我们在多个层面上研究动态行为，包括与ATP结合和水解相关的原子和质子水平的结构变化，如晶体结构所示，以及由内在和外在因素驱动的亚基结合和解离事件。我们研究了来自四个模型系统（T4噬菌体，E. coli、S. cerevisiae和H. sapiens），展示了它们的特性是如何针对这些不同物种的特定环境要求而定制的。我们建议，突触前纤维已经发展到依赖于多种外部因素，以增加多层次的调节HR过程中的基因组具有更大的结构和序列的复杂性。
Homologous Recombination (HR) is an essential genome stability mechanism used for high-fidelity repair of DNA double-strand breaks and for the recovery of stalled or collapsed DNA replication forks. The crucial homology search and DNA strand exchange steps of HR are catalyzed by presynaptic filaments—helical filaments of a recombinase enzyme bound to single-stranded DNA. Presynaptic filaments are fundamentally dynamic structures, the assembly, catalytic turnover, and disassembly of which must be closely coordinated with other elements of the DNA recombination, repair, and replication machinery in order for genome maintenance functions to be effective. Here, we review the major dynamic elements controlling the assembly, activity, and disassembly of presynaptic filaments: some intrinsic such as recombinase ATP binding and hydrolytic activities, others extrinsic such as ssDNA-binding proteins, mediator proteins, and DNA motor proteins. We examine dynamic behavior on multiple levels, including atomic- and filament-level structural changes associated with ATP binding and hydrolysis as evidenced in crystal structures, as well as subunit binding and dissociation events driven by intrinsic and extrinsic factors. We examine the biochemical properties of recombination proteins from four model systems (T4 phage, E. coli, S. cerevisiae, and H. sapiens), demonstrating how their properties are tailored for the context-specific requirements in these diverse species. We propose that the presynaptic filament has evolved to rely on multiple external factors for increased multi-level regulation of HR processes in genomes with greater structural and sequence complexity.
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