1 research outputs found
Mutually Exclusive Formation of G‑Quadruplex and i‑Motif Is a General Phenomenon Governed by Steric Hindrance in Duplex DNA
G-Quadruplex
and i-motif are tetraplex structures that may form
in opposite strands at the same location of a duplex DNA. Recent discoveries
have indicated that the two tetraplex structures can have conflicting
biological activities, which poses a challenge for cells to coordinate.
Here, by performing innovative population analysis on mechanical unfolding
profiles of tetraplex structures in double-stranded DNA, we found
that formations of G-quadruplex and i-motif in the two complementary
strands are mutually exclusive in a variety of DNA templates, which
include human telomere and promoter fragments of hINS and hTERT genes.
To explain this behavior, we placed G-quadruplex- and i-motif-hosting
sequences in an offset fashion in the two complementary telomeric
DNA strands. We found simultaneous formation of the G-quadruplex and
i-motif in opposite strands, suggesting that mutual exclusivity between
the two tetraplexes is controlled by steric hindrance. This conclusion
was corroborated in the BCL-2 promoter sequence, in which simultaneous
formation of two tetraplexes was observed due to possible offset arrangements
between G-quadruplex and i-motif in opposite strands. The mutual exclusivity
revealed here sets a molecular basis for cells to efficiently coordinate
opposite biological activities of G-quadruplex and i-motif at the
same dsDNA location