Cohesins and condensins orchestrate the 4D dynamics of yeast chromosomes during the cell cycle

The duplication and segregation of chromosomes involve the dynamic re-organization of their internal structure by conserved architectural proteins, such as structural maintenance of chromosomes complexes (i.e., cohesin and condensin). Although the roles of these factors is actively investigated, a genome-wide view of chromosome dynamic architecture at both small and large-scales during cell division remains elusive. Here we report the first comprehensive 4D analysis of the Saccharomyces cerevisiae genome higher-order organization during the cell cycle, and investigate the roles of SMC in the observed structural transitions. During replication, cohesion establishment promotes long-range intra-chromosomal contacts and correlates with the individualization of chromosomes, which culminates at metaphase. Mitotic chromosomes are then abruptly reorganized in anaphase by mechanical forces exerted by the mitotic spindle. The formation of a condensin-dependent loop, that bridges the centromere cluster with the rDNA loci, suggests that condensin-mediated forces may also directly facilitate segregation. This work provides a comprehensive overview of chromosome dynamics during the cell cycle of a unicellular eukaryote that recapitulates and unveils new features of highly conserved stages of the cell division.染色体的复制与分离过程，依赖保守的结构蛋白对其内部结构进行动态重排，其中以染色体结构维持复合物（Structural Maintenance of Chromosomes, SMC）——即黏连素（cohesin）与凝缩素（condensin）——为代表。尽管学界正积极探究这些因子的功能，但细胞分裂过程中，染色体动态结构在小尺度与大尺度下的全基因组视角仍有待阐明。本研究首次对酿酒酵母（Saccharomyces cerevisiae）在细胞周期中的基因组高级结构进行了系统性四维分析，并探究了SMC复合物在观测到的结构转变中的作用。在DNA复制阶段，黏连素的建立过程会促进染色体内的远程接触，并与染色体的个体化过程相关联，该过程在细胞分裂中期达到顶峰。随后在有丝分裂后期，有丝分裂纺锤体施加的机械力会使有丝分裂染色体发生剧烈重排。一类桥接连结着丝粒簇与核糖体DNA（rDNA）位点的凝缩素依赖型环的形成，表明凝缩素介导的机械力或许也可直接助力染色体分离过程。本研究全面梳理了单细胞真核生物酿酒酵母细胞周期中的染色体动态变化，该模型不仅重现了高度保守的细胞分裂阶段特征，还揭示了全新的细胞分裂结构特征。