染色体(SMC)蛋白质复合物的结构维持-粘附素,凝集素,和Smc5/6复合物(Smc5/6)-对于染色体功能是必需的。在分子水平上,这些复合物通过环挤压折叠DNA。因此,连环蛋白在间期产生染色体环,凝聚素压缩有丝分裂染色体。然而,Smc5/6最近发现的DNA环挤压活性的作用是未知的。这里,我们发现Smc5/6在芽殖酵母(酿酒酵母)染色体上依赖粘附蛋白的环边界与转录诱导的正超螺旋DNA相关。机械上,单分子成像显示Smc5/6的二聚体特异性识别正超螺旋DNAplectonemes的尖端,并有效地启动环挤出以将超螺旋DNA聚集到大的plectonemic环中。最后,Hi-C分析表明,Smc5/6以顺式连接包含转录诱导的正超螺旋的染色体区域。总之,我们的发现表明,Smc5/6通过识别和启动正超螺旋DNA上的环挤压来控制染色体的三维组织。
The structural maintenance of chromosomes (SMC) protein complexes-cohesin, condensin, and the Smc5/6 complex (Smc5/6)-are essential for chromosome function. At the molecular level, these complexes fold DNA by loop extrusion. Accordingly, cohesin creates chromosome loops in interphase, and condensin compacts mitotic chromosomes. However, the role of Smc5/6\'s recently discovered DNA loop extrusion activity is unknown. Here, we uncover that Smc5/6 associates with transcription-induced positively supercoiled DNA at cohesin-dependent loop boundaries on budding yeast (Saccharomyces cerevisiae) chromosomes. Mechanistically, single-molecule imaging reveals that dimers of Smc5/6 specifically recognize the tip of positively supercoiled DNA plectonemes and efficiently initiate loop extrusion to gather the supercoiled DNA into a large plectonemic loop. Finally, Hi-C analysis shows that Smc5/6 links chromosomal regions containing transcription-induced positive supercoiling in cis. Altogether, our findings indicate that Smc5/6 controls the three-dimensional organization of chromosomes by recognizing and initiating loop extrusion on positively supercoiled DNA.