Fujimura Akiko, Hayashi Yuki, Kato Kazashi, Kogure Yuichiro, Kameyama Mutsuro, Shimamoto Haruka, Daitoku Hiroaki, Fukamizu Akiyoshi, Hirota Toru, Kimura Keiji
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tenno-dai, Tsukuba Science City, Ibaraki 305-8577, Japan.
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tenno-dai, Tsukuba Science City, Ibaraki 305-8577, Japan.
Nucleic Acids Res. 2020 Jul 9;48(12):6583-6596. doi: 10.1093/nar/gkaa449.
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. During mitotic 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.
核仁是一种无膜的核结构,在细胞进行有丝分裂时会解体。因此,在有丝分裂期间,核仁因子从核仁中释放出来,并动态改变其亚细胞定位;然而,它们的功能在很大程度上仍未得到充分表征。在这里,我们发现一种名为核仁蛋白11(NOL11)的核仁因子在有丝分裂细胞中与两种名为WD重复蛋白43(WDR43)和Cirhin的色氨酸-天冬氨酸(WD)重复蛋白形成蛋白质复合物。这种复合物,在这里称为NWC(NOL11-WDR43-Cirhin)复合物,在间期存在于核仁中,并转移到有丝分裂染色体的外围,即染色体周围区域。在有丝分裂进程中,在没有NWC复合物的情况下,染色体向中期板的汇聚和姐妹染色单体的黏附都会受损,因为它是Aurora B着丝粒富集和组蛋白H3苏氨酸3位点相关磷酸化所必需的。这些结果揭示了一种由核仁蛋白组成的新型蛋白质复合物的特征,该复合物是调节动粒和着丝粒以确保染色体忠实分离所必需的。