Identification of a novel nucleolar protein complex required for mitotic chromosome segregation through centromeric accumulation of Aurora B
Identification of a novel nucleolar protein complex required for mitotic chromosome segregation through centromeric accumulation of Aurora B
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DOI：
10.1093/nar/gkaa449
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发表时间：
2020-07-09
影响因子：
14.9
通讯作者：
Kimura, Keiji
中科院分区：
文献类型：
--
作者：
Fujimura, Akiko;Hayashi, Yuki;Kimura, Keiji
核仁是一种无膜核结构，当细胞进行有丝分裂时会分解。在有丝分裂过程中，核仁因子从核仁中释放出来，并动态地改变它们的亚细胞定位；然而，它们的职能在很大程度上仍不明确。在这里，我们发现有丝分裂细胞中一种称为核仁蛋白 11 (NOL11) 的核仁因子与两个名为 WD-重复蛋白 43 (WDR43) 和 Cirhin 的色氨酸-天冬氨酸 (WD) 重复蛋白形成蛋白复合物。该复合体在此称为 NWC (NOL11-WDR43-Cirhin) 复合体，在间期期间存在于核仁中，并易位到有丝分裂染色体的外围，即染色体周围区域。在有丝分裂过程中，在缺乏 NWC 复合体的情况下，染色体向中期板的会聚和姐妹染色单体的内聚力都会受到损害，因为它是 Aurora B 着丝粒富集和组蛋白 H3 在苏氨酸 3 处的相关磷酸化所必需的。这些结果揭示了由核仁蛋白组成的新型蛋白质复合物的特征，该复合物是调节着丝粒和着丝粒以确保可靠的染色体分离所必需的。
The nucleolus is a membrane-less nuclear structure that disassembles when cells undergo mitosis. During mitosis, nucleolar factors are thus released from the nucleolus and dynamically change their subcellular localization; however, their functions remain largely uncharacterised. Here, we found that a nucleolar factor called nucleolar protein 11 (NOL11) forms a protein complex with two tryptophan-aspartic acid (WD) repeat proteins named WD-repeat protein 43 (WDR43) and Cirhin in mitotic cells. This complex, referred to here as the NWC (NOL11-WDR43-Cirhin) complex, exists in nucleoli during interphase and translocates to the periphery of mitotic chromosomes, i.e., perichromosomal regions. Duringmitotic progression, both the congression of chromosomes to the metaphase plate and sister chromatid cohesion are impaired in the absence of the NWC complex, as it is required for the centromeric enrichment of Aurora B and the associating phosphorylation of histone H3 at threonine 3. These results reveal the characteristics of a novel protein complex consisting of nucleolar proteins, which is required for regulating kinetochores and centromeres to ensure faithful chromosome segregation.