Rad52反向链交换驱动RNA模板化的DNA双链断裂修复。
Rad52 Inverse Strand Exchange Drives RNA-Templated DNA Double-Strand Break Repair.
作者信息
Mazina Olga M, Keskin Havva, Hanamshet Kritika, Storici Francesca, Mazin Alexander V
机构信息
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
出版信息
Mol Cell. 2017 Jul 6;67(1):19-29.e3. doi: 10.1016/j.molcel.2017.05.019. Epub 2017 Jun 8.
RNA can serve as a template for DNA double-strand break repair in yeast cells, and Rad52, a member of the homologous recombination pathway, emerged as an important player in this process. However, the exact mechanism of how Rad52 contributes to RNA-dependent DSB repair remained unknown. Here, we report an unanticipated activity of yeast and human Rad52: inverse strand exchange, in which Rad52 forms a complex with dsDNA and promotes strand exchange with homologous ssRNA or ssDNA. We show that in eukaryotes, inverse strand exchange between homologous dsDNA and RNA is a distinctive activity of Rad52; neither Rad51 recombinase nor the yeast Rad52 paralog Rad59 has this activity. In accord with our in vitro results, our experiments in budding yeast provide evidence that Rad52 inverse strand exchange plays an important role in RNA-templated DSB repair in vivo.
RNA可作为酵母细胞中DNA双链断裂修复的模板，同源重组途径的成员Rad52在这一过程中成为重要角色。然而，Rad52如何促进依赖RNA的双链断裂修复的确切机制仍不清楚。在此，我们报道了酵母和人类Rad52的一种意外活性：反向链交换，即Rad52与双链DNA形成复合物，并促进与同源单链RNA或单链DNA的链交换。我们表明，在真核生物中，同源双链DNA与RNA之间的反向链交换是Rad52的一种独特活性；Rad51重组酶和酵母Rad52旁系同源物Rad59都没有这种活性。与我们的体外实验结果一致，我们在芽殖酵母中的实验提供了证据，表明Rad52反向链交换在体内RNA模板的双链断裂修复中起重要作用。
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