Control of meiotic crossover interference by a proteolytic chaperone network
Control of meiotic crossover interference by a proteolytic chaperone network
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DOI：
10.1038/s41477-024-01633-y
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发表时间：
2024-02-20
期刊：
影响因子：
18
通讯作者：
Choi，Kyuha
中科院分区：
文献类型：
--
作者：
Kim，Heejin;Kim，Jaeil;Choi，Kyuha
减数分裂是真核生物的一种专门化分裂，为有性繁殖产生遗传多样性的配子。在减数分裂期间，同源染色体配对并经历相互交换，称为交叉，这种交换重组遗传变异。减数分裂交换受到严格控制，每对染色体至少形成一个专有交换，而紧密排列的交换则受到干扰的抑制。在拟南芥中，交叉位置可以用扩散介导的粗化模型来解释，在该模型中，前交叉E3连接酶HEI10的大的、大致均匀分布的焦点以较小的、紧密分布的簇为代价生长。然而，在减数分裂过程中控制HEI10动态的机制仍然不清楚。在这里，通过在拟南芥中的正向遗传筛选，我们发现了高交叉率3(Hcr3)，这是一个显性-负向突变体，减少了交叉干扰，增加了全基因组范围的交叉。hcr3编码J3，它是一种与Hsp40相关的辅助伴侣蛋白，它作用于蛋白质聚集体和生物分子缩合物到分解伴侣HSP70，从而促进蛋白酶体的降解。我们一贯地表明，HCR3和HSP70伴侣的网络促进了HEI10的蛋白分解，从而调节了干扰和重组景观。这些结果揭示了Hsp40/J3-HSP70伴侣蛋白通过控制HEI10蛋白降解来调节整个染色体的重组动力学的新作用。
Meiosis is a specialized eukaryotic division that produces genetically diverse gametes for sexual reproduction. During meiosis, homologous chromosomes pair and undergo reciprocal exchanges, called crossovers, which recombine genetic variation. Meiotic crossovers are stringently controlled with at least one obligate exchange forming per chromosome pair, while closely spaced crossovers are inhibited by interference. InArabidopsis, crossover positions can be explained by a diffusion-mediated coarsening model, in which large, approximately evenly spaced foci of the pro-crossover E3 ligase HEI10 grow at the expense of smaller, closely spaced clusters. However, the mechanisms that control HEI10 dynamics during meiosis remain unclear. Here, through a forward genetic screen inArabidopsis, we identifiedhigh crossover rate3(hcr3), a dominant-negative mutant that reduces crossover interference and increases crossovers genome-wide.HCR3encodes J3, a co-chaperone related to HSP40, which acts to target protein aggregates and biomolecular condensates to the disassembly chaperone HSP70, thereby promoting proteasomal degradation. Consistently, we show that a network of HCR3 and HSP70 chaperones facilitates proteolysis of HEI10, thereby regulating interference and the recombination landscape. These results reveal a new role for the HSP40/J3-HSP70 chaperones in regulating chromosome-wide dynamics of recombination via control of HEI10 proteolysis.