Abstract:
Accurate duplication and separation of long linear genomic DNA molecules is associated with a number of purely mechanical problems. SMC complexes are key components of the cellular machinery that ensures decatenation of sister chromosomes and compaction of genomic DNA during division. Cohesin, one of the essential eukaryotic SMC complexes, has a typical ring structure with intersubunit pore through which DNA molecules can be threaded. Capacity of cohesin for such topological entrapment of DNA is crucial for the phenomenon of post-replicative association of sister chromatids better known as cohesion. Recently, it became apparent that cohesin and other SMC complexes are, in fact, motor proteins with a very peculiar movement pattern leading to formation of DNA loops. This specific process has been called loop extrusion. Extrusion underlies multiple functions of cohesin beyond cohesion, but molecular mechanism of the process remains a mystery. In this review, we summarized the data on molecular architecture of cohesin, effect of ATP hydrolysis cycle on this architecture, and known modes of cohesin-DNA interactions. Many of the seemingly disparate facts presented here will probably be incorporated in a unified mechanistic model of loop extrusion in the not-so-distant future.
摘要:
长线性基因组DNA分子的精确复制和分离与许多纯机械问题有关。SMC复合物是细胞机制的关键组成部分,可确保在分裂过程中姐妹染色体的缺失和基因组DNA的压缩。Cohesin,一种重要的真核SMC复合物,具有典型的环结构,具有亚基间孔,DNA分子可以穿过该孔。粘附素进行这种DNA拓扑捕获的能力对于姐妹染色单体的复制后缔合现象至关重要,这通常被称为内聚。最近,很明显,cohesin和其他SMC复合物是,事实上,具有非常特殊的运动模式的马达蛋白,导致DNA环的形成。这个特定的过程被称为环挤出。挤压是凝聚的多种功能的基础,但是这个过程的分子机制仍然是个谜。在这次审查中,我们总结了粘附蛋白的分子结构数据,ATP水解循环对这种结构的影响,和已知的粘附蛋白-DNA相互作用模式。在不远的将来,这里提出的许多看似完全不同的事实可能会被纳入一个统一的循环挤压机械模型中。