Structural Diversity of Supercoiled DNA

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Oct 13

PMID 26455586

Citations 83

Authors

Rossitza N Irobalieva

Jonathan M Fogg

Daniel J Catanese Jr

Daniel J Catanese

Thana Sutthibutpong

Muyuan Chen

Anna K Barker

Steven J Ludtke

Sarah A Harris

Michael F Schmid

Wah Chiu

Lynn Zechiedrich

Affiliations

Soon will be listed here.

Abstract

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA minicircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function.

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