Kaur Hardeep, De Muyt Arnaud, Lichten Michael
Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.
Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.
Mol Cell. 2015 Feb 19;57(4):583-594. doi: 10.1016/j.molcel.2015.01.020.
The topoisomerase III (Top3)-Rmi1 heterodimer, which catalyzes DNA single-strand passage, forms a conserved complex with the Bloom's helicase (BLM, Sgs1 in budding yeast). This complex has been proposed to regulate recombination by disassembling double Holliday junctions in a process called dissolution. Top3-Rmi1 has been suggested to act at the end of this process, resolving hemicatenanes produced by earlier BLM/Sgs1 activity. We show here that, to the contrary, Top3-Rmi1 acts in all meiotic recombination functions previously associated with Sgs1, most notably as an early recombination intermediate chaperone, promoting regulated crossover and noncrossover recombination and preventing aberrant recombination intermediate accumulation. In addition, we show that Top3-Rmi1 has important Sgs1-independent functions that ensure complete recombination intermediate resolution and chromosome segregation. These findings indicate that Top3-Rmi1 activity is important throughout recombination to resolve strand crossings that would otherwise impede progression through both early steps of pathway choice and late steps of intermediate resolution.
拓扑异构酶III(Top3)-Rmi1异二聚体可催化DNA单链通过,它与布鲁姆解旋酶(BLM,在芽殖酵母中为Sgs1)形成保守复合物。有人提出,该复合物通过在一个称为解离的过程中拆解双霍利迪连接体来调节重组。有人认为Top3-Rmi1在这一过程的末期发挥作用,解决早期BLM/Sgs1活性产生的半连环体。我们在此表明,恰恰相反,Top3-Rmi1在所有先前与Sgs1相关的减数分裂重组功能中都发挥作用,最显著的是作为早期重组中间体伴侣,促进调控交叉和非交叉重组,并防止异常重组中间体积累。此外,我们表明Top3-Rmi1具有重要的不依赖Sgs1的功能,可确保完全解决重组中间体并实现染色体分离。这些发现表明,Top3-Rmi1的活性在整个重组过程中都很重要,可解决链交叉问题,否则这些链交叉会在途径选择的早期步骤和中间体解决的后期步骤中阻碍进程。