Register-Shifted Structures in Base-Flipped Uracil-Damaged DNA

J Am Chem Soc. 2023 Aug 2;145(30):16350-16354. doi: 10.1021/jacs.3c05890. Epub 2023 Jul 21.

Abstract

We report the occurrence of register-shifted structures in simulations of uracil-containing dsDNA. These occur when the 3' base vicinal to uracil is thymine in U:A base-paired DNA. Upon base flipping of uracil, this 3' thymine hydrogen bonds with the adenine across the uracil instead of its complementary base. The register-shifted structure is persistent and sterically blocks re-entry of uracil into the helix stack. Register shifting might be important for DNA repair since the longer exposure of the lesion in register-shifted structures could facilitate enzymatic recognition and repair.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • DNA / chemistry
  • DNA Damage
  • DNA Repair
  • Thymine* / chemistry
  • Uracil* / chemistry
  • Uracil-DNA Glycosidase / chemistry

Substances

  • Uracil
  • Thymine
  • Uracil-DNA Glycosidase
  • DNA