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Competitive superhelical transitions involving cruciform extrusion
Dina Zhabinskaya1, Craig J Benham
1UC Davis Genome Center, University of California, One Shields Avenue, Davis, CA 95616, USA.
Nucleic Acids Research
|August 24, 2013
Summary
DNA supercoiling can induce alternate structures like cruciforms. Longer inverted repeats (IRs) favor cruciform extrusion, potentially driving chromosomal translocations, but are rare in gene regulatory regions.
Area of Science:
- Molecular Biology
- Genetics
- Biophysics
Background:
- DNA molecules under negative superhelical stress can adopt alternative structures.
- The specific conformations depend on the DNA base sequence and compete for stability.
- Previous methods allowed calculation of equilibrium distributions and thermodynamic properties for DNA systems.
Purpose of the Study:
- To extend computational methods for analyzing DNA structures to include cruciform extrusion.
- To investigate cruciform extrusion at both perfect and imperfect inverted repeat (IR) sequences.
- To assess the role of cruciform formation in gene regulation and chromosomal rearrangements.
Main Methods:
- Development of a computational method to calculate equilibrium distributions of DNA conformations.
- Extension of the method to model superhelical cruciform extrusion at IR sequences.
- Analysis of IR length, sequence, and competition with other DNA structures (strand separation, B-Z transitions).
Main Results:
- Short IRs do not readily extrude cruciforms, even without competition.
- As IR length increases, cruciform extrusion can become the dominant conformation.
- Extrusion-susceptible IRs are infrequent in human DNA and generally avoid transcription start sites.
- Susceptibility of long IRs at translocation breakpoints to cruciform formation correlates with observed translocation frequencies.
Conclusions:
- Cruciform extrusion is sequence and length-dependent, becoming significant for longer IRs.
- Cruciform formation is unlikely to be a widespread mechanism for gene regulation in eukaryotes.
- Cruciform extrusion is a plausible mechanism driving chromosomal translocations at specific long IRs.
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