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RecQ和拓扑异构酶III对收敛复制叉的解析

Resolution of converging replication forks by RecQ and topoisomerase III.

作者信息

Suski Catherine, Marians Kenneth J

机构信息

Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.

出版信息

Mol Cell. 2008 Jun 20;30(6):779-89. doi: 10.1016/j.molcel.2008.04.020.

Abstract

RecQ-like DNA helicases pair with cognate topoisomerase III enzymes to function in the maintenance of genomic integrity in many organisms. These proteins play roles in stabilizing stalled replication forks, the S phase checkpoint response, and suppressing genetic crossovers, and their inactivation results in hyper-recombination, gross chromosomal rearrangements, chromosome segregation defects, and human disease. Biochemical activities associated with these enzymes include the ability to resolve double Holliday junctions, a process thought to lead to the suppression of crossover formation. Using Escherichia coli RecQ and topoisomerase III, we demonstrate a second activity for this pair of enzymes that could account for their role in maintaining genomic stability: resolution of converging replication forks. This resolution reaction is specific for the RecQ-topoisomerase III pair and is mediated by interaction of both of these enzymes with the single-stranded DNA-binding protein SSB.

摘要

类RecQ DNA解旋酶与同源拓扑异构酶III结合,在许多生物体中维持基因组完整性方面发挥作用。这些蛋白质在稳定停滞的复制叉、S期检查点反应以及抑制基因交换中发挥作用,它们的失活会导致超重组、大规模染色体重排、染色体分离缺陷以及人类疾病。与这些酶相关的生化活性包括解决双Holliday连接的能力,这一过程被认为会导致交叉形成的抑制。利用大肠杆菌RecQ和拓扑异构酶III,我们证明了这对酶的第二种活性,这可以解释它们在维持基因组稳定性中的作用:解决汇聚的复制叉。这种解决反应对RecQ-拓扑异构酶III对具有特异性,并且由这两种酶与单链DNA结合蛋白SSB的相互作用介导。

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本文引用的文献

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Binding and activation of DNA topoisomerase III by the Rmi1 subunit.Rmi1亚基对DNA拓扑异构酶III的结合与激活
J Biol Chem. 2007 Sep 28;282(39):28971-28979. doi: 10.1074/jbc.M705427200. Epub 2007 Aug 9.
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Role of the BLM helicase in replication fork management.BLM解旋酶在复制叉管理中的作用。
DNA Repair (Amst). 2007 Jul 1;6(7):936-44. doi: 10.1016/j.dnarep.2007.02.007. Epub 2007 Mar 23.
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RecQ helicases: lessons from model organisms.RecQ解旋酶:来自模式生物的经验教训。
Nucleic Acids Res. 2006;34(15):4106-14. doi: 10.1093/nar/gkl557. Epub 2006 Aug 26.

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