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Twisting tetraplex DNA: A strand dynamics regulating i-motif function in diverse molecular crowding environments.

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Molecular crowding influences DNA i-motif stability and function. Specific polyethylene glycols (PEGs) and oligoethylene glycols (OEGs) with six or more units stabilize i-motif DNA, impacting gene regulation.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Intercalated motif (i-motif) tetraplex DNA is vital for gene expression and disease.
  • Limited knowledge exists on i-motif regulation within cells due to few identified binding proteins.
  • Cellular molecular environments are hypothesized to be key regulators of i-motif formation and function.

Purpose of the Study:

  • To investigate how diverse molecular crowding environments affect i-motif DNA stability and function.
  • To elucidate the chemical mechanisms underlying i-motif regulation by molecular environments.

Main Methods:

  • Systematic investigation using various polyethylene glycols (PEGs) and oligoethylene glycols (OEGs) to mimic cellular crowding.
  • Quantitative validation through nuclear magnetic resonance (NMR) and molecular dynamics simulations.
  • Assessment of hypochromicity changes and solution properties.

Main Results:

  • PEGs and OEGs with six or more ethylene glycol units significantly stabilized the human telomere i-motif.
  • Shorter PEGs/OEGs (less than six units) destabilized the i-motif.
  • Cosolute-induced twisting dynamics altered the activation energy barrier for replication by a twofold magnitude.

Conclusions:

  • Molecular environments, specifically crowding agents like PEGs and OEGs, play a significant role in regulating i-motif DNA stability and function.
  • The length of ethylene glycol units in crowding agents dictates the stabilization or destabilization of i-motif structures.
  • These findings suggest potential regulatory mechanisms for i-motif biological roles across cellular phases mediated by the molecular environment.