Structure and conformational dynamics of a stacked dimeric G-quadruplex formed by the human CEB1 minisatellite

J Am Chem Soc. 2014 Apr 30;136(17):6297-305. doi: 10.1021/ja4125274. Epub 2014 Apr 17.


CEB1 is a highly polymorphic human minisatellite. In yeast, the size variation of CEB1 tandem arrays has been associated with the capacity of the motif to form G-quadruplexes. Here we report on the NMR solution structure of a G-quadruplex formed by the CEB1 DNA G-rich fragment d(AGGGGGGAGGGAGGGTGG), harboring several G-tracts including one with six continuous guanines. This sequence forms a dimeric G-quadruplex involving the stacking of two subunits, each being a unique snapback parallel-stranded scaffold with three G-tetrad layers, three double-chain-reversal loops, and a V-shaped loop. The two subunits are stacked at their 5'-end tetrads, and multiple stacking rotamers may be present due to a high symmetry at the stacking interface. There is a conformational exchange in the millisecond time scale involving a swapping motion between two bases of the six-guanine tract. Our results not only add to the understanding of how the G-quadruplex formation in human minisatellite leads to genetic instability but also address the fundamental questions regarding stacking of G-quadruplexes and how a long continuous G-tract participates in the structure and conformational dynamics of G-quadruplexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA / chemistry*
  • DNA / genetics
  • G-Quadruplexes*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Minisatellite Repeats*
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular


  • HERC5 protein, human
  • Intracellular Signaling Peptides and Proteins
  • DNA