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

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

Author information

1
School of Physical and Mathematical Sciences, Nanyang Technological University , Singapore 637371, Singapore.

Abstract

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.

PMID:
24742225
DOI:
10.1021/ja4125274
[Indexed for MEDLINE]

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