Abstract:
The compaction of chromatin into mitotic chromosomes is essential for faithful transmission of the genome during cell division. In eukaryotes, chromosome morphogenesis is regulated by the condensin complex, though the exact mechanism used to target condensin to chromatin and initiate condensation is not understood. Here, we reveal that condensin contains an intrinsically disordered region (IDR) that modulates its association with chromatin in early mitosis and exhibits phase separation. We describe DNA-binding motifs within the IDR that, upon deletion, inflict striking defects in chromosome condensation and segregation, ill-timed condensin turnover on chromatin, and cell death. Importantly, we demonstrate that the condensin IDR can impart cell cycle regulatory functions when transferred to other subunits within the complex, indicating its autonomous nature. Collectively, our study unveils the molecular basis for the initiation of chromosome condensation in early mitosis and how this process ultimately promotes genomic stability and faultless cell division.
摘要:
染色质压缩为有丝分裂染色体对于细胞分裂过程中基因组的忠实传递至关重要。在真核生物中,染色体形态发生是由凝聚素复合物调节的,尽管用于将凝缩素靶向染色质并引发缩合的确切机制尚不清楚。这里,我们发现凝缩蛋白包含一个内在无序区域(IDR),该区域在有丝分裂早期调节其与染色质的关联并表现出相分离。我们描述了IDR中的DNA结合基序,删除后,在染色体凝聚和分离中造成显著的缺陷,染色质上的凝缩素周转时间不当,细胞死亡。重要的是,我们证明了凝缩素IDR在转移到复合物中的其他亚基时可以赋予细胞周期调节功能,表明其自主性。总的来说,我们的研究揭示了在有丝分裂早期染色体凝聚的分子基础,以及这个过程如何最终促进基因组的稳定性和无缺陷的细胞分裂。