ATP Hydrolysis Coordinates the Activities of Two Motors in a Dimeric Chromatin Remodeling Enzyme

ATP-dependent chromatin remodelers are essential enzymes that restructure eukaryotic genomes to enable all DNA-based processes. The diversity and complexity of these processes arethe complexity of the enzymes that carry them out, making remodelers a challenging class of molecular motors to study by conventional methods. Here we use a single molecule biophysical assay to overcome some of these challenges, enabling a detailed mechanistic dissection of a paradigmatic remodeler reaction, that of sliding a nucleosome towards the longer DNA linker. We focus on how two motors of a dimeric remodeler coordinate to accomplish such directional sliding. We find that ATP hydrolysis by both motors promotes coordination, suggesting a role for ATP in resolving the competition for directional commitment. Furthermore, we show an artificially constitutive dimer is no more or less coordinated, but is more processive, suggesting a cell could modulate a remodeler's oligomeric state to modulate local chromatin dynamics. (c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

In this study, a single molecule biophysical assay was used to investigate the mechanism of chromatin remodelers. The results showed that ATP hydrolysis by the molecular motors promoted coordination and played a key role in directional sliding.