SMC motor proteins extrude DNA asymmetrically and contain a direction switch

Author:

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

Abstract

SummaryStructural Maintenance of Chromosomes (SMC) complexes organize the genomeviaDNA loop extrusion. While 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 usingin vitrosingle-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, while 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. STAG1 stabilizes NIPBL on cohesin, preventing NIPBL turnover and direction switches. The findings reveal that SMCs, surprisingly, contain a direction switch subunit.HighlightsAll eukaryotic SMC complexes extrude DNA asymmetrically.Apparent ‘symmetric’ loop extrusion is the result of frequent direction switches.n human cohesin, loop-extrusion direction changes require exchange of NIPBL.STAG1 stabilizes NIPBL on human cohesin.

Publisher

Cold Spring Harbor Laboratory

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