Jeon Hyuk-Joon, Oh Jeong Su
Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, South Korea.
Front Cell Dev Biol. 2021 Sep 17;9:749116. doi: 10.3389/fcell.2021.749116. eCollection 2021.
In eukaryotic chromosomes, the centromere and telomere are two specialized structures that are essential for chromosome stability and segregation. Although centromeres and telomeres often are located in close proximity to form telocentric chromosomes in mice, it remained unclear whether these two structures influence each other. Here we show that TRF1 is required for inner centromere and kinetochore assembly in addition to its role in telomere protection in mouse oocytes. TRF1 depletion caused premature chromosome segregation by abrogating the spindle assembly checkpoint (SAC) and impairing kinetochore-microtubule (kMT) attachment, which increased the incidence of aneuploidy. Notably, TRF1 depletion disturbed the localization of Survivin and Ndc80/Hec1 at inner centromeres and kinetochores, respectively. Moreover, SMC3 and SMC4 levels significantly decreased after TRF1 depletion, suggesting that TRF1 is involved in chromosome cohesion and condensation. Importantly, inhibition of inner centromere or kinetochore function led to a significant decrease in TRF1 level and telomere shortening. Therefore, our results suggest that telomere integrity is required to preserve inner centromere and kinetochore architectures, and vice versa, suggesting mutual regulation between telomeres and centromeres.
在真核生物染色体中，着丝粒和端粒是两个特殊结构，对染色体的稳定性和分离至关重要。尽管在小鼠中着丝粒和端粒常常紧密相邻形成端着丝粒染色体，但这两个结构是否相互影响仍不清楚。在此我们表明，在小鼠卵母细胞中，TRF1除了在端粒保护中发挥作用外，对于内着丝粒和动粒组装也是必需的。TRF1缺失通过废除纺锤体组装检查点（SAC）和损害动粒-微管（kMT）附着导致染色体过早分离，这增加了非整倍体的发生率。值得注意的是，TRF1缺失分别扰乱了Survivin和Ndc80/Hec1在内着丝粒和动粒处的定位。此外，TRF1缺失后SMC3和SMC4水平显著降低，表明TRF1参与染色体黏连和凝聚。重要的是，抑制内着丝粒或动粒功能导致TRF1水平显著降低和端粒缩短。因此，我们的结果表明端粒完整性对于维持内着丝粒和动粒结构是必需的，反之亦然，这表明端粒和着丝粒之间存在相互调节。
