Eukaryotic resectosomes: A single-molecule perspective.
Eukaryotic resectosomes: A single-molecule perspective.
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DOI：
10.1016/j.pbiomolbio.2016.08.001
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发表时间：
2017-08
影响因子：
3.8
通讯作者：
Finkelstein IJ
中科院分区：
文献类型：
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作者：
Myler LR;Finkelstein IJ
DNA双链断裂（DSB）破坏了基因组的物理和遗传连续性。如果不修复，DSB可导致细胞功能障碍和恶性转化。同源重组（HR）是一种普遍保守的DSB修复机制，它利用姐妹染色单体中的信息来催化无错误的DSB修复。为了启动HR，细胞组装切除体：由解旋酶、核酸酶和调节蛋白组成的多蛋白复合物。切除体核裂解降解（切除）游离DNA末端用于下游同源重组。几十年的深入研究已经确定了真核生物，古细菌和细菌中的核心切除体成分。最近，这些蛋白质已经通过单分子方法进行了表征。在这里，我们专注于最近的单分子研究，已经开始解开核酸酶，解旋酶，持续合成因子和其他调控蛋白如何决定真核细胞中DNA切除的程度和效率。最后，我们讨论了可以通过单分子方法解决的悬而未决的问题。
DNA double-strand breaks (DSBs) disrupt the physical and genetic continuity of the genome. If unrepaired, DSBs can lead to cellular dysfunction and malignant transformation. Homologous recombination (HR) is a universally conserved DSB repair mechanism that employs the information in a sister chromatid to catalyze error-free DSB repair. To initiate HR, cells assemble the resectosome: a multi-protein complex composed of helicases, nucleases, and regulatory proteins. The resectosome nucleolytically degrades (resects) the free DNA ends for downstream homologous recombination. Several decades of intense research have identified the core resectosome components in eukaryotes, archaea, and bacteria. More recently, these proteins have been characterized via single-molecule approaches. Here, we focus on recent single-molecule studies that have begun to unravel how nucleases, helicases, processivity factors, and other regulatory proteins dictate the extent and efficiency of DNA resection in eukaryotic cells. We conclude with a discussion of outstanding questions that can be addressed via single-molecule approaches.