Visualizing cell-cell communication using synthetic notch activated MRI
Visualizing cell-cell communication using synthetic notch activated MRI
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DOI：
10.1073/pnas.2310542120
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发表时间：
2023-03-01
影响因子：
11.1
通讯作者：
Ronald，John A.
中科院分区：
文献类型：
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作者：
Wang，TianDuo;Chen，Yuanxin;Ronald，John A.
在减数分裂或交换（CO）期间，同源染色体之间的DNA相互交换会打乱配子和后代中的遗传信息。在许多真核生物中，大多数CO（I类CO）对一种称为干扰的现象敏感，这种现象会影响紧密间隔的双CO的发生。I类CO依赖于一组称为ZMM（Zip，Msh，Mer）蛋白的因子，包括HEI 10（Human Enhancer of Invasion-10）。然而，这些蛋白质是如何被募集到I类CO位点的尚不清楚。在这里，我们表明HEI 10通过依赖于残基Ser 70的液-液相分离（LLPS）机制在染色质上形成焦点。HEI 10 S70 F等位基因导致LLPS失效和I类CO形成缺陷。我们进一步使用免疫沉淀-质谱法来鉴定RPA 1a（复制蛋白A 1）作为HEI 10相互作用蛋白。令人惊讶的是，我们发现RPA 1a也发生相分离，其遍在化和降解直接受HEI 10调节。我们还表明，HEI 10所需的其他I类CO因子的冷凝。因此，我们的研究结果提供了机械的洞察减数分裂I类CO的形成是如何控制的HEI 10耦合LLPS和泛素化。
Reciprocal exchanges of DNA between homologous chromosomes during meiosis, or crossovers (COs), shuffle genetic information in gametes and progeny. In many eukaryotes, the majority of COs (class I COs) are sensitive to a phenomenon called interference, which influences the occurrence of closely spaced double COs. Class I COs depend on a group of factors called ZMM (Zip, Msh, Mer) proteins including HEI10 (Human Enhancer of Invasion-10). However, how these proteins are recruited to class I CO sites is unclear. Here, we show that HEI10 forms foci on chromatin via a liquid–liquid phase separation (LLPS) mechanism that relies on residue Ser70. A HEI10S70Fallele results in LLPS failure and a defect in class I CO formation. We further used immunoprecipitation–mass spectrometry to identify RPA1a (Replication Protein A 1) as a HEI10 interacting protein. Surprisingly, we find that RPA1a also undergoes phase separation and its ubiquitination and degradation are directly regulated by HEI10. We also show that HEI10 is required for the condensation of other class I CO factors. Thus, our results provide mechanistic insight into how meiotic class I CO formation is controlled by HEI10 coupling LLPS and ubiquitination.