A Minimal Sequence for Left-Handed G-Quadruplex Formation

Angew Chem Int Ed Engl. 2019 Feb 18;58(8):2331-2335. doi: 10.1002/anie.201812628. Epub 2019 Jan 21.

Abstract

Recently, we observed the first example of a left-handed G-quadruplex structure formed by natural DNA, named Z-G4. We analysed the Z-G4 structure and inspected its primary 28-nt sequence in order to identify motifs that convey the unique left-handed twist. Using circular dichroism spectroscopy, NMR spectroscopy, and X-ray crystallography, we revealed a minimal sequence motif of 12 nt (GTGGTGGTGGTG) for formation of the left-handed DNA G-quadruplex, which is found to be highly abundant in the human genome. A systematic analysis of thymine loop mutations revealed a moderate sequence tolerance, which would further broaden the space of sequences prone to left-handed G-quadruplex formation.

Keywords: DNA; DNA structures; G-quadruplexes; X-ray diffraction; circular dichroism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • DNA / chemistry*
  • G-Quadruplexes*
  • Humans
  • Models, Molecular

Substances

  • DNA