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人类Rad51核蛋白在单个DNA分子上动力学的直接成像

Direct imaging of human Rad51 nucleoprotein dynamics on individual DNA molecules.

作者信息

Hilario Jovencio, Amitani Ichiro, Baskin Ronald J, Kowalczykowski Stephen C

机构信息

Departments of Microbiology and Molecular and Cellular Biology, University of California, Davis, CA 95616-8665, USA.

出版信息

Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):361-8. doi: 10.1073/pnas.0811965106. Epub 2009 Jan 2.

Abstract

Rad51 protein (Rad51) is central to recombinational repair of double-strand DNA breaks. It polymerizes onto DNA and promotes strand exchange between homologous chromosomes. We visualized the real-time assembly and disassembly of human Rad51 nucleoprotein filaments on double-stranded DNA by single-molecule fluorescence microscopy. Rad51 assembly extends the DNA by approximately 65%. Nucleoprotein filament formation occurs via rapid nucleation followed by growth from these nuclei. Growth does not continue indefinitely, however, and nucleoprotein filaments terminate when approximately 2 mum in length. The dependence of nascent filament formation on Rad51 concentration suggests that 2-3 Rad51 monomers are involved in nucleation. Rad51 nucleoprotein filaments are stable and remain extended when ATP hydrolysis is prevented; however, when permitted, filaments decrease in length as a result of conversion to ADP-bound nucleoprotein complexes and partial protein dissociation. Dissociation of Rad51 from dsDNA is slow and incomplete, thereby rationalizing the need for other proteins that facilitate disassembly.

摘要

Rad51蛋白在双链DNA断裂的重组修复过程中起着核心作用。它能聚合到DNA上,并促进同源染色体之间的链交换。我们通过单分子荧光显微镜观察了人Rad51核蛋白细丝在双链DNA上的实时组装和解聚过程。Rad51组装使DNA延长约65%。核蛋白细丝的形成是通过快速成核,然后从这些核开始生长。然而,生长不会无限期持续,当长度约为2μm时,核蛋白细丝就会终止。新生细丝形成对Rad51浓度的依赖性表明,成核过程涉及2 - 3个Rad51单体。当ATP水解被阻止时,Rad51核蛋白细丝是稳定的且保持伸展状态;然而,如果允许ATP水解,细丝会因转化为结合ADP的核蛋白复合物和部分蛋白质解离而缩短。Rad51从双链DNA上的解离缓慢且不完全,因此解释了为何需要其他促进解聚的蛋白质。

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本文引用的文献

1
RecBCD enzyme switches lead motor subunits in response to chi recognition.
Cell. 2007 Nov 16;131(4):694-705. doi: 10.1016/j.cell.2007.09.023.
2
Real-time assembly and disassembly of human RAD51 filaments on individual DNA molecules.
Nucleic Acids Res. 2007;35(17):5646-57. doi: 10.1093/nar/gkm629. Epub 2007 Aug 20.
3
Single molecule imaging of Tid1/Rdh54, a Rad54 homolog that translocates on duplex DNA and can disrupt joint molecules.
J Biol Chem. 2007 Oct 19;282(42):30776-84. doi: 10.1074/jbc.M704767200. Epub 2007 Aug 16.
5
Direct observation of individual RecA filaments assembling on single DNA molecules.
Nature. 2006 Oct 19;443(7113):875-8. doi: 10.1038/nature05197. Epub 2006 Sep 20.
6
Tid1/Rdh54 promotes dissociation of Dmc1 from nonrecombinogenic sites on meiotic chromatin.
Genes Dev. 2006 Sep 15;20(18):2593-604. doi: 10.1101/gad.1447106.
8
Visualizing the assembly of human Rad51 filaments on double-stranded DNA.
J Mol Biol. 2006 Oct 27;363(3):713-28. doi: 10.1016/j.jmb.2006.08.046. Epub 2006 Aug 22.
9
Mechanism of RecA-mediated homologous recombination revisited by single molecule nanomanipulation.
EMBO J. 2006 Sep 20;25(18):4293-304. doi: 10.1038/sj.emboj.7601260. Epub 2006 Aug 31.
10
Unraveling helicase mechanisms one molecule at a time.
Nucleic Acids Res. 2006;34(15):4225-31. doi: 10.1093/nar/gkl452. Epub 2006 Aug 25.

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