DNA tension-modulated translocation and loop extrusion by SMC complexes revealed by molecular dynamics simulations.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_6486FE868A87
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
DNA tension-modulated translocation and loop extrusion by SMC complexes revealed by molecular dynamics simulations.
Journal
Nucleic acids research
Author(s)
Nomidis S.K., Carlon E., Gruber S., Marko J.F.
ISSN
1362-4962 (Electronic)
ISSN-L
0305-1048
Publication state
Published
Issued date
20/05/2022
Peer-reviewed
Oui
Volume
50
Number
9
Pages
4974-4987
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Structural Maintenance of Chromosomes (SMC) complexes play essential roles in genome organization across all domains of life. To determine how the activities of these large (≈50 nm) complexes are controlled by ATP binding and hydrolysis, we developed a molecular dynamics model that accounts for conformational motions of the SMC and DNA. The model combines DNA loop capture with an ATP-induced 'power stroke' to translocate the SMC complex along DNA. This process is sensitive to DNA tension: at low tension (0.1 pN), the model makes loop-capture steps of average 60 nm and up to 200 nm along DNA (larger than the complex itself), while at higher tension, a distinct inchworm-like translocation mode appears. By tethering DNA to an experimentally-observed additional binding site ('safety belt'), the model SMC complex can perform loop extrusion (LE). The dependence of LE on DNA tension is distinct for fixed DNA tension vs. fixed DNA end points: LE reversal occurs above 0.5 pN for fixed tension, while LE stalling without reversal occurs at about 2 pN for fixed end points. Our model matches recent experimental results for condensin and cohesin, and makes testable predictions for how specific structural variations affect SMC function.
Keywords
Adenosine Triphosphate/metabolism, Cell Cycle Proteins/metabolism, Chromosomes/metabolism, DNA/chemistry, Humans, Molecular Conformation, Molecular Dynamics Simulation, Translocation, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
02/05/2022 12:33
Last modification date
02/02/2023 6:52
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