A twist defect mechanism for ATP-dependent translocation of nucleosomal DNA

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Abstract

As superfamily 2 (SF2)-type translocases, chromatin remodelers are expected to use an inchworm-type mechanism to walk along DNA. Yet how they move DNA around the histone core has not been clear. Here we show that a remodeler ATPase motor can shift large segments of DNA by changing the twist and length of nucleosomal DNA at superhelix location 2 (SHL2). Using canonical and variant 601 nucleosomes, we find that the Saccharomyces cerevisiae Chd1 remodeler decreased DNA twist at SHL2 in nucleotide-free and ADP-bound states, and increased twist with transition state analogs. These differences in DNA twist allow the open state of the ATPase to pull in ~1 base pair (bp) by stabilizing a small DNA bulge, and closure of the ATPase to shift the DNA bulge toward the dyad. We propose that such formation and elimination of twist defects underlie the mechanism of nucleosome sliding by CHD-, ISWI-, and SWI/SNF-type remodelers.

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Extended gel images are given in figure supplements.

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Jessica Winger

T C Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Ilana M Nodelman

T C Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Robert F Levendosky

T C Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Gregory D Bowman

T C Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, United States

For correspondence
gdbowman@jhu.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8025-4315

Funding

National Institutes of Health (R01-GM084192)

Jessica Winger
Ilana M Nodelman
Robert F Levendosky
Gregory D Bowman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.