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黏连蛋白和凝聚蛋白在细胞周期中协调酵母染色体的四维动态变化。

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

作者信息

Lazar-Stefanita Luciana, Scolari Vittore F, Mercy Guillaume, Muller Héloise, Guérin Thomas M, Thierry Agnès, Mozziconacci Julien, Koszul Romain

机构信息

Institut Pasteur, Department Genomes and Genetics, Unité Régulation Spatiale des Génomes, Paris, France.

CNRS, UMR 3525, Paris, France.

出版信息

EMBO J. 2017 Sep 15;36(18):2684-2697. doi: 10.15252/embj.201797342. Epub 2017 Jul 20.

DOI:10.15252/embj.201797342
PMID:28729434
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5599795/
Abstract

Duplication and segregation of chromosomes involves dynamic reorganization of their internal structure by conserved architectural proteins, including the structural maintenance of chromosomes (SMC) complexes cohesin and condensin. Despite active investigation of the roles of these factors, a genome-wide view of dynamic chromosome architecture at both small and large scale during cell division is still missing. Here, we report the first comprehensive 4D analysis of the higher-order organization of the genome throughout the cell cycle and investigate the roles of SMC complexes in controlling structural transitions. During replication, cohesion establishment promotes numerous long-range intra-chromosomal contacts and correlates with the individualization of chromosomes, which culminates at metaphase. In anaphase, mitotic chromosomes are abruptly reorganized depending on mechanical forces exerted by the mitotic spindle. Formation of a condensin-dependent loop bridging the centromere cluster with the rDNA loci suggests that condensin-mediated forces may also directly facilitate segregation. This work therefore comprehensively recapitulates cell cycle-dependent chromosome dynamics in a unicellular eukaryote, but also unveils new features of chromosome structural reorganization during highly conserved stages of cell division.

摘要

染色体的复制和分离涉及由保守的结构蛋白对其内部结构进行动态重组，这些蛋白包括染色体结构维持（SMC）复合物黏连蛋白和凝聚蛋白。尽管对这些因子的作用进行了积极研究，但在细胞分裂过程中，从微观和宏观层面全面了解动态染色体结构的研究仍付之阙如。在此，我们报告了对整个细胞周期中基因组高阶组织的首次全面四维分析，并研究了SMC复合物在控制结构转变中的作用。在复制过程中，黏连的建立促进了大量的远距离染色体内接触，并与染色体的个体化相关，这在中期达到顶峰。在后期，有丝分裂染色体根据有丝分裂纺锤体施加的机械力突然重组。形成一个依赖凝聚蛋白的环，将着丝粒簇与核糖体DNA位点连接起来，这表明凝聚蛋白介导的力也可能直接促进分离。因此，这项工作全面概括了单细胞真核生物中依赖细胞周期的染色体动态变化，同时也揭示了细胞分裂高度保守阶段染色体结构重组的新特征。

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