An Overview of the Molecular Mechanisms of Recombinational DNA Repair

An Overview of the Molecular Mechanisms of Recombinational DNA Repair
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DOI:
10.1101/cshperspect.a016410
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发表时间:
2015-11-01
影响因子:
7.2
通讯作者:
Kowalczykowski, Stephen C.
Kowalczykowski, Stephen C.
中科院分区:
生物学1区
文献类型:
--
作者:
Kowalczykowski, Stephen C.

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破坏性DNA修复是DNA代谢的一个普遍方面,对基因组完整性至关重要。这是一个模板导向的过程,使用第二个染色体拷贝(姐妹,女儿或同源物),以确保正确修复断裂的染色体。重组的关键步骤是保守的从噬菌体到人类,这些步骤的概述提供了在这篇评论。第一步是通过解旋酶和核酸酶切除以产生定义同源基因座的单链DNA(ssDNA)。ssDNA是RecA/RAD 51细丝组装的支架,其促进同源性搜索。在发现同源性时,核蛋白丝催化DNA链的交换以形成一个连接分子。通过调节RecA/RAD 51细丝和DNA配对中间体的命运来控制降解。最后,成熟为霍利迪结构的中间体通过溶核分解或拓扑溶解而分离。
Recombinational DNA repair is a universal aspect of DNA metabolism and is essential for genomic integrity. It is a template-directed process that uses a second chromosomal copy (sister, daughter, or homolog) to ensure proper repair of broken chromosomes. The key steps of recombination are conserved from phage through human, and an overview of those steps is provided in this review. The first step is resection by helicases and nucleases to produce single-stranded DNA (ssDNA) that defines the homologous locus. The ssDNA is a scaffold for assembly of the RecA/RAD51 filament, which promotes the homology search. On finding homology, the nucleoprotein filament catalyzes exchange of DNA strands to form a joint molecule. Recombination is controlled by regulating the fate of both RecA/RAD51 filaments and DNA pairing intermediates. Finally, intermediates that mature into Holliday structures are disjoined by either nucleolytic resolution or topological dissolution.