Genome Damage and Stability Centre, Science Park Road, University of Sussex, Falmer, Brighton, East Sussex BN1 9RQ, UK.
Bioessays. 2019 Jan;41(1):e1800182. doi: 10.1002/bies.201800182. Epub 2018 Dec 3.
The extreme length of chromosomal DNA requires organizing mechanisms to both promote functional genetic interactions and ensure faithful chromosome segregation when cells divide. Microscopy and genome-wide contact frequency analyses indicate that intra-chromosomal looping of DNA is a primary pathway of chromosomal organization during all stages of the cell cycle. DNA loop extrusion has emerged as a unifying model for how chromosome loops are formed in cis in different genomic contexts and cell cycle stages. The highly conserved family of SMC complexes have been found to be required for DNA cis-looping and have been suggested to be the enzymatic core of loop extruding machines. Here, the current body of evidence available for the in vivo and in vitro action of SMC complexes is discussed and compared to the predictions made by the loop extrusion model. How SMC complexes may differentially act on chromatin to generate DNA loops and how they could work to generate the dynamic and functionally appropriate organization of DNA in cells is explored.
染色体 DNA 的极端长度需要组织机制来促进功能遗传相互作用，并确保细胞分裂时染色体的正确分离。显微镜和全基因组接触频率分析表明，在细胞周期的所有阶段，染色体 DNA 的环内回环是染色体组织的主要途径。DNA 环外推已成为一种统一的模型，用于解释在不同基因组背景和细胞周期阶段中如何在顺式中形成染色体环。高度保守的 SMC 复合物家族已被发现是 DNA 顺式环形成所必需的，并被认为是环外推机器的酶核心。本文讨论了 SMC 复合物在体内和体外的作用的现有证据，并将其与环外推模型的预测进行了比较。SMC 复合物如何在染色质上差异作用以产生 DNA 环，以及它们如何工作以产生细胞中 DNA 的动态和功能适当的组织，这是值得探索的。
