奥地利维也纳生物中心分子病理研究所Jan-Michael Peters研究组研究发现DNA被人类黏附素挤压成环。这一研究成果2019年11月21日在线发表在《科学》杂志上。

他们表示，使用生化重构，单个人黏附素复合物以每秒高达2.1 kbp的速度对称地形成DNA环。环的形成和维持依赖于黏附素的ATP酶活性和NIPBL-MAU2，而不依赖于黏附素对DNA的拓扑构象的捕获。在形成环的过程中，黏附素和NIPBL-MAU2位于环的底部，表明它们通过挤压生成环。

他们的结果表明，黏附素和NIPBL-MAU2形成了一种活性全酶，该酶与DNA进行伪拓扑或非拓扑构象相互作用，从而将基因组间期DNA挤出成环。

据悉，真核基因组被折叠成环和拓扑相关结构域（TAD），它们有助于染色质结构，基因调控和重组。这些结构依赖于黏附素，黏附素是一种环状DNA捕获ATP酶复合物，已被提出通过挤压形成环。在凝缩素中观察到了这样的活性，它在有丝分裂中形成环，而对于黏附素则没有。

附：英文原文

Title: DNA loop extrusion by human cohesin

Author: Iain F. Davidson, Benedikt Bauer, Daniela Goetz, Wen Tang, Gordana Wutz, Jan-Michael Peters

Issue&Volume: 2019/11/21

Abstract: Eukaryotic genomes are folded into loops and topologically-associating domains (TADs), which contribute to chromatin structure, gene regulation and recombination. These structures depend on cohesin, a ring-shaped DNA-entrapping ATPase complex which has been proposed to form loops by extrusion. Such an activity has been observed for condensin, which forms loops in mitosis, but not for cohesin. Here we show, using biochemical reconstitution, that single human cohesin complexes form DNA loops symmetrically at up to 2.1 kbp per second. Loop formation and maintenance depend on cohesin’s ATPase activity and on NIPBL-MAU2, but not on topological entrapment of DNA by cohesin. During loop formation, cohesin and NIPBL-MAU2 reside at the base of loops, indicating that they generate loops by extrusion. Our results show that cohesin and NIPBL-MAU2 form an active holo-enzyme that interacts with DNA either pseudo-topologically or non-topologically to extrude genomic interphase DNA into loops.

DOI: 10.1126/science.aaz3418

Source: https://science.sciencemag.org/content/early/2019/11/20/science.aaz3418