美国康奈尔大学Michelle D. Wang课题组最新研究发现了染色质扭转力学与拓扑异构酶活性的协同协调。 该项研究成果发表在2019年10月17日出版的《细胞》上。

通过进行直接扭矩测量，研究人员证明了，染色质内在机械性能在决定前索烃的形成和调节染色质拓扑方面起着基本作用。单个染色质纤维具有扭转软性，而编织纤维具有扭转刚性，这表明在复制过程中，染色质基质上的超卷曲形成早于复制叉。进一步表明，与编织纤维相比，松弛态的拓扑异构酶II具有对单个染色质纤维的强烈偏好性。

这些结果表明了一种协同作用——染色质的机械特性相协调在复制叉形成前驱动DNA超螺旋来抑制复制延伸过程中前索烃的形成。这表明拓扑异构酶II可更有效地去除超螺旋。

研究人员表示，真核生物中DNA复制产生DNA超螺旋，该超螺旋可能使子染色质纤维交织（编织）形成前索烃，从而在染色体分离过程中造成拓扑难题。然而，限制前索烃形成的机制仍不清楚。

附：英文原文

Title: Synergistic Coordination of Chromatin Torsional Mechanics and Topoisomerase Activity

Author: Tung T. Le, Xiang Gao, Seong ha Park, Jaeyoon Lee, James T. Inman, Joyce H. Lee, Jessica L. Killian, Ryan P. Badman, James M. Berger, Michelle D. Wang

Issue&Volume: 2019/10/17

Abstract: 

DNA replication in eukaryotes generates DNA supercoiling, which may intertwine (braid) daughter chromatin fibers to form precatenanes, posing topological challenges during chromosome segregation. The mechanisms that limit precatenane formation remain unclear. By making direct torque measurements, we demonstrate that the intrinsic mechanical properties of chromatin play a fundamental role in dictating precatenane formation and regulating chromatin topology. Whereas a single chromatin fiber is torsionally soft, a braided fiber is torsionally stiff, indicating that supercoiling on chromatin substrates is preferentially directed in front of the fork during replication. We further show that topoisomerase II relaxation displays a strong preference for a single chromatin fiber over a braided fiber. These results suggest a synergistic coordination—the mechanical properties of chromatin inherently suppress precatenane formation during replication elongation by driving DNA supercoiling ahead of the fork, where supercoiling is more efficiently removed by topoisomerase II.

DOI: 10.1016/j.cell.2019.09.034

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31115-8