2024-12-13 オランダ・デルフト工科大学(TUDelft)
<関連情報>
- https://www.tudelft.nl/en/2024/tnw/a-new-twist-the-molecular-machines-that-loop-our-chromosomes-also-twist-dna
- https://www.science.org/doi/10.1126/sciadv.adt1832
すべての真核生物のSMCタンパク質は、DNAループの押し出しステップごとに-0.6のねじれを引き起こす All eukaryotic SMC proteins induce a twist of -0.6 at each DNA loop extrusion step
Richard Janissen, Roman Barth, Iain F. Davidson, Jan-Michael Peters, and Cees Dekker
Science Advances Published:13 Dec 2024
DOI:https://doi.org/10.1126/sciadv.adt1832
Abstract
Eukaryotes carry three types of structural maintenance of chromosome (SMC) protein complexes, condensin, cohesin, and SMC5/6, which are ATP-dependent motor proteins that remodel the genome via DNA loop extrusion (LE). SMCs modulate DNA supercoiling but remains incompletely understood how this is achieved. Using a single-molecule magnetic tweezers assay that directly measures how much twist is induced by individual SMCs in each LE step, we demonstrate that all three SMC complexes induce the same large negative twist (i.e., linking number change ΔLk of ~-0.6 at each LE step) into the extruded loop, independent of step size and DNA tension. Using ATP hydrolysis mutants and nonhydrolyzable ATP analogs, we find that ATP binding is the twist-inducing event during the ATPase cycle, coinciding with the force-generating LE step. The fact that all three eukaryotic SMC proteins induce the same amount of twist indicates a common DNA-LE mechanism among these SMC complexes.