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DNA Dynamics Is Likely to Be a Factor in the Genomic Nucleotide Repeats Expansions Related to Diseases
by Boian S. Alexandrov, Vlad I. Valtchinov, Ludmil B. Alexandrov, Vladimir Gelev, Yossi Dagon, Jonathan Bock, Isaac S. Kohane, Kim Ø. Rasmussen, Alan R. Bishop, Anny Usheva
Trinucleotide repeats sequences (TRS) represent a common type of genomic DNA
motif whose expansion is associated with a large number of human diseases. The
driving molecular mechanisms of the TRS ongoing dynamic expansion across
generations and within tissues and its influence on genomic DNA functions are
not well understood. Here we report results for a novel and notable collective
breathing behavior of genomic DNA of tandem TRS, leading to propensity for large
local DNA transient openings at physiological temperature. Our Langevin
molecular dynamics (LMD) and Markov Chain Monte Carlo (MCMC) simulations
demonstrate that the patterns of openings of various TRSs depend specifically on
their length. The collective propensity for DNA strand separation of repeated
sequences serves as a precursor for outsized intermediate bubble states
independently of the G/C-content. We report that repeats have the potential to
interfere with the binding of transcription factors to their consensus sequence
by altered DNA breathing dynamics in proximity of the...
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- Molecular models of DNA - Wikipedia, the free encyclopedia
Molecular models of DNA structures are representations of the molecular geometry and topology of Deoxyribonucleic acid (DNA) molecules using one of several means ...
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