title: Structure and conformational dynamics of a stacked dimeric G-quadruplex formed by the human CEB1 minisatellite.
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.
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University , Singapore 637371, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Adrian
authors.forename: Ding Jie
authors.initials: DJ
authors.lastname: Ang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lech
authors.forename: Brahim
authors.initials: B
authors.lastname: Heddi
authors.forename: Alain
authors.initials: A
authors.lastname: Nicolas
authors.forename: Anh Tuân
authors.initials: AT
authors.lastname: Phan
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D054856:G-Quadruplexes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D018598:Minisatellite Repeats; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: C402395:HERC5 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D004247:DNA