Influence of DNA sequence on the structure of minicircles under torsional stress

Qian Wang, Rossitza N. Irobalieva, Wah Chiu, Michael F. Schmid, Jonathan M. Fogg, Lynn Zechiedrich, B. Montgomery Pettitt

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The sequence dependence of the conformational distribution of DNA under various levels of torsional stress is an important unsolved problem. Combining theory and coarse-grained simulations shows that the DNA sequence and a structural correlation due to topology constraints of a circle are the main factors that dictate the 3D structure of a 336 bp DNA minicircle under torsional stress. We found that DNA minicircle topoisomers can have multiple bend locations under high torsional stress and that the positions of these sharp bends are determined by the sequence, and by a positive mechanical correlation along the sequence. We showed that simulations and theory are able to provide sequence-specific information about individual DNA minicircles observed by cryo-electron tomography (cryo-ET). We provided a sequence-specific cryo-ET tomogram fitting of DNA minicircles, registering the sequence within the geometric features. Our results indicate that the conformational distribution of minicircles under torsional stress can be designed, which has important implications for using minicircle DNA for gene therapy.

Original languageEnglish (US)
Pages (from-to)7633-7642
Number of pages10
JournalNucleic acids research
Volume45
Issue number13
DOIs
StatePublished - Jul 1 2017

ASJC Scopus subject areas

  • Genetics

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    Wang, Q., Irobalieva, R. N., Chiu, W., Schmid, M. F., Fogg, J. M., Zechiedrich, L., & Pettitt, B. M. (2017). Influence of DNA sequence on the structure of minicircles under torsional stress. Nucleic acids research, 45(13), 7633-7642. https://doi.org/10.1093/nar/gkx516