荷兰代尔夫特理工大学Cees Dekker团队近期取得重要工作进展，他们研究提出，SMC马达蛋白以不对称方式挤出DNA且能够切换方向。相关研究成果2025年1月16日在线发表于《细胞》杂志上。

据介绍，染色体结构维持（SMC）复合物通过DNA环挤出过程来组织基因组。尽管此前有报道称，一些SMC复合物能够以对称方式进行这一过程，即同时从两侧将DNA卷入挤出的DNA环中，但也有其他复合物仅以不对称方式朝着一个方向进行环挤出。这种差异背后的机制尚不清楚。

研究人员通过体外单分子实验研究了SMC复合物对DNA环挤出的方向性。研究人员发现，黏连蛋白和SMC5/6并非如之前所报道的那样从两侧卷入DNA，而是以不对称方式挤出DNA，尽管其方向会随时间发生切换。因此，不对称DNA环挤出是所有真核生物SMC复合物的共同机制。对于黏连蛋白而言，方向的切换与亚基NIPBL的更替密切相关，在此过程中可能会发生DNA链的切换。除了通过挤出过程扩张，DNA环还经常发生扩散和收缩。

总之，这一研究揭示了SMC复合物能够切换方向。

附：英文原文

Title: SMC motor proteins extrude DNA asymmetrically and can switch directions

Author: Roman Barth, Iain F. Davidson, Jaco van der Torre, Michael Taschner, Stephan Gruber, Jan-Michael Peters, Cees Dekker

Issue&Volume: 2025-01-16

Abstract: Structural maintenance of chromosomes (SMC) complexes organize the genome via DNA loop extrusion. Although some SMCs were reported to do so symmetrically, reeling DNA from both sides into the extruded DNA loop simultaneously, others perform loop extrusion asymmetrically toward one direction only. The mechanism underlying this variability remains unclear. Here, we examine the directionality of DNA loop extrusion by SMCs using in vitro single-molecule experiments. We find that cohesin and SMC5/6 do not reel in DNA from both sides, as reported before, but instead extrude DNA asymmetrically, although the direction can switch over time. Asymmetric DNA loop extrusion thus is the shared mechanism across all eukaryotic SMC complexes. For cohesin, direction switches strongly correlate with the turnover of the subunit NIPBL, during which DNA strand switching may occur. Apart from expanding by extrusion, loops frequently diffuse and shrink. The findings reveal that SMCs, surprisingly, can switch directions.

DOI: 10.1016/j.cell.2024.12.020

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01433-8