Cooperative kinking at distant sites in mechanically stressed DNA

In cells, DNA is routinely subjected to significant levels of bending and twisting. In some cases, such as under physiological levels of supercoiling, DNA can be so highly strained, that it transitions into non-canonical structural conformations that are capable of relieving mechanical stress within...

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Published inNucleic acids research Vol. 39; no. 22; pp. 9820 - 9832
Main Authors Lionberger, Troy A., Demurtas, Davide, Witz, Guillaume, Dorier, Julien, Lillian, Todd, Meyhöfer, Edgar, Stasiak, Andrzej
Format Journal Article
LanguageEnglish
Published England Oxford University Press 01.12.2011
Subjects
Brownian motion
Conformation
Cooperativity
Cryoelectron Microscopy
DNA structure
DNA, Circular - chemistry
DNA, Circular - ultrastructure
Endodeoxyribonucleases
Free energy
Models, Molecular
Nucleic Acid Conformation
Stress
Stress, Mechanical
Structural Biology
Supercoiling
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Summary:In cells, DNA is routinely subjected to significant levels of bending and twisting. In some cases, such as under physiological levels of supercoiling, DNA can be so highly strained, that it transitions into non-canonical structural conformations that are capable of relieving mechanical stress within the template. DNA minicircles offer a robust model system to study stress-induced DNA structures. Using DNA minicircles on the order of 100 bp in size, we have been able to control the bending and torsional stresses within a looped DNA construct. Through a combination of cryo-EM image reconstructions, Bal31 sensitivity assays and Brownian dynamics simulations, we have been able to analyze the effects of biologically relevant underwinding-induced kinks in DNA on the overall shape of DNA minicircles. Our results indicate that strongly underwound DNA minicircles, which mimic the physical behavior of small regulatory DNA loops, minimize their free energy by undergoing sequential, cooperative kinking at two sites that are located about 180° apart along the periphery of the minicircle. This novel form of structural cooperativity in DNA demonstrates that bending strain can localize hyperflexible kinks within the DNA template, which in turn reduces the energetic cost to tightly loop DNA.
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Present address: Troy A. Lionberger, Howard Hughes Medical Institute and Jason L. Choy Laboratory of Single-Molecule Biophysics, Department of Physics, University of California, Berkeley, CA 94720, USA. Guillaume Witz, Department of Molecular and Cellular Biology, Harvard University, Cambridge MA 02138, USA.
The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkr666