A Central Coupler for Recombination Initiation Linking Chromosome Architecture to S Phase Checkpoint
A Central Coupler for Recombination Initiation Linking Chromosome Architecture to S Phase Checkpoint
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DOI：
10.1016/j.molcel.2012.06.023
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发表时间：
2012-09-14
期刊：
影响因子：
16
通讯作者：
Ohta, Kunihiro
中科院分区：
文献类型：
--
作者：
Miyoshi, Tomoichiro;Ito, Masaru;Ohta, Kunihiro
高阶染色体结构被认为控制真核生物中各种dna模板化反应。减数分裂染色体具有称为“轴”和“环”的发达结构；两者相互束缚，激活Spoil在重组热点催化减数分裂DNA双链断裂（DSBs）。我们发现裂糖菌pombe Spo11同源物Red 12及其伙伴形成两个不同的亚复合物，DSBC （Rec6-Rec12-Rec14）和SFT （Rec7-Rec15-Rec24）。Mde2的表达受到复制检查点的严格调控，它与Rec15相互作用以稳定SFT亚复合物，并进一步结合DSBC中的Rec14。Rec10为SFT结合轴提供了一个对接平台，并且可以根据Mde2与位于环中的DSB位点部分相互作用，这表明形成了基于多蛋白的系固轴-环复合物。这些数据使我们提出了一种机制，通过该机制，Mde2作为重组起始介质，与减数分裂复制检查点联系，连接轴和环。
Higher-order chromosome structure is assumed to control various DNA-templated reactions in eukaryotes. Meiotic chromosomes implement developed structures called "axes" and "loops"; both are suggested to tether each other, activating Spoil to catalyze meiotic DNA double-strand breaks (DSBs) at recombination hotspots. We found that the Schizosaccharomyces pombe Spo11 homolog Red 12 and its partners form two distinct subcomplexes, DSBC (Rec6-Rec12-Rec14) and SFT (Rec7-Rec15-Rec24). Mde2, whose expression is strictly regulated by the replication checkpoint, interacts with Rec15 to stabilize the SFT subcomplex and further binds Rec14 in DSBC. Rec10 provides a docking platform for SFT binding to axes and can partially interact with DSB sites located in loops depending upon Mde2, which is indicative of the formation of multiprotein-based tethered axis-loop complex. These data lead us to propose a mechanism by which Mde2 functions as a recombination initiation mediator to tether axes and loops, in liaison with the meiotic replication checkpoint.