Proline-rich protein PRR19 functions with cyclin-like CNTD1 to promote meiotic crossing over in mouse
Proline-rich protein PRR19 functions with cyclin-like CNTD1 to promote meiotic crossing over in mouse
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DOI：
10.1038/s41467-020-16885-3
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发表时间：
2020-06-18
影响因子：
16.6
通讯作者：
Toth, Attila
中科院分区：
文献类型：
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作者：
Bondarieva, Anastasiia;Raveendran, Kavya;Toth, Attila
在第一次减数分裂中同源染色体间的交叉使有序的染色体分离成为可能。交叉产生于重组介导的程序性DNA双链断裂（DSBs）修复。多个dsb启动重组，大多数在没有交叉形成的情况下被修复，尽管每条染色体上有一个或多个产生交叉。尽管其潜在机制尚不明确，但交叉特异性重组中间体的分化和成熟需要细胞周期蛋白样CNTD1。在这里，我们确定PRR19是CNTD1的合作伙伴。我们发现，与CNTD1一样，PRR19也是及时修复DSB和形成跨特异性重组复合物所必需的。PRR19和CNTD1在交叉位点共同定位，物理上相互作用，并且相互依赖积累，表明PRR19-CNTD1在交叉过程中是伙伴关系。此外，我们发现CNTD1与周期蛋白依赖性激酶CDK2相互作用，CDK2也在交叉特异性重组复合物中积累。因此，PRR19-CNTD1复合体可能通过调节CDK2实现交叉分化。杂交是减数分裂过程中的一个关键过程，尽管这个过程的调控仍然有些难以捉摸。在这里，作者表明PRR19与CNTD1合作，在小鼠生殖细胞中形成交叉特异性重组复合物。
Orderly chromosome segregation is enabled by crossovers between homologous chromosomes in the first meiotic division. Crossovers arise from recombination-mediated repair of programmed DNA double-strand breaks (DSBs). Multiple DSBs initiate recombination, and most are repaired without crossover formation, although one or more generate crossovers on each chromosome. Although the underlying mechanisms are ill-defined, the differentiation and maturation of crossover-specific recombination intermediates requires the cyclin-like CNTD1. Here, we identify PRR19 as a partner of CNTD1. We find that, like CNTD1, PRR19 is required for timely DSB repair and the formation of crossover-specific recombination complexes. PRR19 and CNTD1 co-localise at crossover sites, physically interact, and are interdependent for accumulation, indicating a PRR19-CNTD1 partnership in crossing over. Further, we show that CNTD1 interacts with a cyclin-dependent kinase, CDK2, which also accumulates in crossover-specific recombination complexes. Thus, the PRR19-CNTD1 complex may enable crossover differentiation by regulating CDK2. Crossing over is a critical process during meiosis, although the regulation of this process still remains somewhat elusive. Here, the authors show that PRR19 partners with CNTD1 to enable formation of crossover-specific recombination complexes in mouse germ cells.