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Nat Commun. 2015 Oct 12;6:8440. doi: 10.1038/ncomms9440.

Structural diversity of supercoiled DNA.

Author information

1
Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030 USA.
2
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 USA.
3
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030 USA.
4
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030 USA.
5
School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, UK.

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.

PMID:
26455586
PMCID:
PMC4608029
DOI:
10.1038/ncomms9440
[Indexed for MEDLINE]
Free PMC Article

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