Supercoiling and Looping Promote DNA Base Accessibility and Coordination Among Distant Sites

Authors

Jonathan M Fogg
Allison K Judge
Erik Stricker
Hilda L Chan
Lynn Zechiedrich

Publication Date

9-28-2021

Journal

Nature Communications

DOI

10.1038/s41467-021-25936-2

PMID

34584096

PMCID

PMC8478907

PubMedCentral® Posted Date

9-28-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Base Pairing, DNA Cleavage, DNA Repair, DNA, Superhelical, Endodeoxyribonucleases, Genomic Instability, Models, Chemical, Models, Genetic, Stress, Mechanical, DNA, Molecular conformation, DNA metabolism, DNA nanostructures

Abstract

DNA in cells is supercoiled and constrained into loops and this supercoiling and looping influence every aspect of DNA activity. We show here that negative supercoiling transmits mechanical stress along the DNA backbone to disrupt base pairing at specific distant sites. Cooperativity among distant sites localizes certain sequences to superhelical apices. Base pair disruption allows sharp bending at superhelical apices, which facilitates DNA writhing to relieve torsional strain. The coupling of these processes may help prevent extensive denaturation associated with genomic instability. Our results provide a model for how DNA can form short loops, which are required for many essential processes, and how cells may use DNA loops to position nicks to facilitate repair. Furthermore, our results reveal a complex interplay between site-specific disruptions to base pairing and the 3-D conformation of DNA, which influences how genomes are stored, replicated, transcribed, repaired, and many other aspects of DNA activity.

Comments

Associated Data