Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils. Jeppsson et al

Published: 18 January 2024| Version 1 | DOI: 10.17632/xm79hh8p65.1
Kristian Jeppsson, Biswajit Pradhan, Takashi Sutani, Toyonori Sakata, Miki Umeda Igarashi, Davide Giorgio Berta, Takaharu Kanno, Ryuichiro Nakato, Katsuhiko Shirahige, Eugene Kim, Camilla Björkegren


The Structural Maintenance of Chromosome (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 initiates 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.



Molecular Biology, Biophysics, Chromosome Structure