8 Henrietta Szold St., The Azrieli Faculty of Medicine, Bar-Ilan University, P.O. Box 1589 Safed, Israel.
8 Henrietta Szold St., The Azrieli Faculty of Medicine, Bar-Ilan University, P.O. Box 1589 Safed, Israel
J Cell Sci. 2021 Jan 8;134(1):jcs247577. doi: 10.1242/jcs.247577.
The three-dimensional structure of chromatin is determined by the action of protein complexes of the structural maintenance of chromosome (SMC) family. Eukaryotic cells contain three SMC complexes, cohesin, condensin, and a complex of Smc5 and Smc6. Initially, cohesin was linked to sister chromatid cohesion, the process that ensures the fidelity of chromosome segregation in mitosis. In recent years, a second function in the organization of interphase chromatin into topologically associated domains has been determined, and loop extrusion has emerged as the leading mechanism of this process. Interestingly, fundamental mechanistic differences exist between mitotic tethering and loop extrusion. As distinct molecular switches that aim to suppress loop extrusion in different biological contexts have been identified, we hypothesize here that loop extrusion is the default biochemical activity of cohesin and that its suppression shifts cohesin into a tethering mode. With this model, we aim to provide an explanation for how loop extrusion and tethering can coexist in a single cohesin complex and also apply it to the other eukaryotic SMC complexes, describing both similarities and differences between them. Finally, we present model-derived molecular predictions that can be tested experimentally, thus offering a new perspective on the mechanisms by which SMC complexes shape the higher-order structure of chromatin.
染色质的三维结构取决于结构维持染色体（SMC）家族的蛋白质复合物的作用。真核细胞包含三种 SMC 复合物，即黏合蛋白、凝聚蛋白和 Smc5 和 Smc6 复合物。最初，黏合蛋白与姐妹染色单体黏合有关，该过程确保有丝分裂中染色体分离的保真度。近年来，已确定黏合蛋白在将染色质组织成拓扑相关结构域方面的第二个功能，并且环挤出已成为该过程的主要机制。有趣的是，有丝分裂固定和环挤出之间存在基本的机制差异。由于已经确定了不同生物背景下旨在抑制环挤出的不同分子开关，因此我们在这里假设环挤出是黏合蛋白的默认生化活性，其抑制将黏合蛋白转变为固定模式。通过该模型，我们旨在解释环挤出和固定如何在单个黏合蛋白复合物中共存，并将其应用于其他真核 SMC 复合物，描述它们之间的相似之处和差异。最后，我们提出了可通过实验测试的基于模型的分子预测，从而为 SMC 复合物塑造染色质高级结构的机制提供了新的视角。
