德国马克斯普朗克生物物理研究所Eugene Kim等研究人员合作发现，Smc5/6复合物是一种DNA环挤压马达。2023年4月19日，《自然》杂志在线发表了这一最新研究成果。

使用单分子成像，研究人员表明Smc5/6通过挤压形成DNA环。在ATP水解后，Smc5/6以每秒一千个碱基对的力依赖性速度将DNA对称地卷成环。Smc5/6以二聚体的形式挤出环，而单体的Smc5/6则沿着DNA单向转移。研究人员还发现，Nse5和Nse6（Nse5/6）亚单位作为环挤压的负调节器。Nse5/6通过阻碍Smc5/6二聚体化来抑制环挤压的启动，但对正在进行的环挤压没有影响。这些研究结果揭示了Smc5/6在分子水平上的功能，并确立了DNA环挤压是真核生物染色体的结构维持（SMC）复合体中的一个保守机制。

据介绍，SMC蛋白复合物对染色体的空间组织至关重要。虽然粘连蛋白和凝集蛋白通过挤压DNA环来组织染色体，但第三种真核生物SMC复合物Smc5/6的分子功能在很大程度上仍是未知的。

附：英文原文

Title: The Smc5/6 complex is a DNA loop-extruding motor

Author: Pradhan, Biswajit, Kanno, Takaharu, Umeda Igarashi, Miki, Loke, Mun Siong, Baaske, Martin Dieter, Wong, Jan Siu Kei, Jeppsson, Kristian, Bjrkegren, Camilla, Kim, Eugene

Issue&Volume: 2023-04-19

Abstract: Structural maintenance of chromosomes (SMC) protein complexes are essential for the spatial organization of chromosomes1. Whereas cohesin and condensin organize chromosomes by extrusion of DNA loops, the molecular functions of the third eukaryotic SMC complex, Smc5/6, remain largely unknown2. Using single-molecule imaging, we show that Smc5/6 forms DNA loops by extrusion. Upon ATP hydrolysis, Smc5/6 reels DNA symmetrically into loops at a force-dependent rate of one kilobase pair per second. Smc5/6 extrudes loops in the form of dimers, whereas monomeric Smc5/6 unidirectionally translocates along DNA. We also find that the subunits Nse5 and Nse6 (Nse5/6) act as negative regulators of loop extrusion. Nse5/6 inhibits loop-extrusion initiation by hindering Smc5/6 dimerization but has no influence on ongoing loop extrusion. Our findings reveal functions of Smc5/6 at the molecular level and establish DNA loop extrusion as a conserved mechanism among eukaryotic SMC complexes.

DOI: 10.1038/s41586-023-05963-3

Source: https://www.nature.com/articles/s41586-023-05963-3