Prevalent Sequences in the Human Genome Can Form Mini i-Motif Structures at Physiological pH

J Am Chem Soc. 2017 Oct 11;139(40):13985-13988. doi: 10.1021/jacs.7b07383. Epub 2017 Sep 27.

Abstract

We report here the solution structure of several repetitive DNA sequences containing d(TCGTTCCGT) and related repeats. At physiological pH, these sequences fold into i-motif like quadruplexes in which every two repeats a globular structure is stabilized by two hemiprotonated C:C+ base pairs, flanked by two minor groove tetrads resulting from the association of G:C or G:T base pairs. The interaction between the minor groove tetrads and the nearby C:C+ base pairs affords a strong stabilization, which results in effective pHT values above 7.5. Longer sequences with more than two repeats are able to fold in tandem, forming a rosary bead-like structure. Bioinformatics analysis shows that these sequences are prevalent in the human genome, and are present in development-related genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing
  • Base Sequence
  • DNA / chemistry*
  • G-Quadruplexes
  • Genome, Human*
  • Humans
  • Hydrogen-Ion Concentration
  • Models, Molecular
  • Nucleic Acid Conformation
  • Repetitive Sequences, Nucleic Acid*

Substances

  • DNA