Unraveling the Kinetics of Spare-Tire DNA G-Quadruplex Folding

J Am Chem Soc. 2021 Apr 28;143(16):6185-6193. doi: 10.1021/jacs.1c01089. Epub 2021 Apr 19.

Abstract

The folding of DNA G-quadruplexes (G4) is essential to regulate expression of oncogenes and involves polymorphic long-lived intermediate states. G4 formation requires four G-tracts, but human gene-promoters often contain multiple G-tracts that act as spare-tires. These additional G-tracts are highly conserved and add multiple layers of functional complexity, as they are crucial to maintain G4 function after oxidative damage. Herein, we unravel the folding dynamics of the G4 sequence containing five G-tracts from cMYC, the major proliferation-driving oncogene. We devise a general method to induce folding at constant experimental conditions using a photochemical trapping strategy. Our data dissect the individual kinetics and thermodynamics of the spare-tire mechanism of cMYC-G4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • G-Quadruplexes*
  • Humans
  • Isomerism
  • Kinetics
  • Nucleic Acid Conformation
  • Proto-Oncogene Proteins c-myc / genetics
  • Thermodynamics

Substances

  • Proto-Oncogene Proteins c-myc