Hilario Jovencio, Amitani Ichiro, Baskin Ronald J, Kowalczykowski Stephen C
Departments of Microbiology and Molecular and Cellular Biology, University of California, Davis, CA 95616-8665, USA.
Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):361-8. doi: 10.1073/pnas.0811965106. Epub 2009 Jan 2.
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.
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。