4 research outputs found
Effects of Polyamine Binding on the Stability of DNA i-Motif Structures
B-form DNA can adopt alternative structures under conditions such as superhelical duress. Alternative DNA structures are favored when there is asymmetric distribution of guanosine and cytosine on complimentary DNA strands. A guanosine-rich strand can form a four-stranded structure known as a quadruplex (G4). The complimentary cytosine-rich strand can utilize intercalating cytosine−cytosine base pairing to form a four-stranded structure known as the i-motif (iM). Both secondary structures are energetically uphill from double-strand DNA (dsDNA), meaning that additional factors are needed for their formation. Most iMs require slightly acidic conditions for structure stabilization. However, crowding agents such as polyethylene glycols and dextrans can shift the pKa of the iM to near-physiological pH ≈ 7. Nucleic acids have long been known to be bound and stabilized by polyamines such as putrescine, spermidine, and spermine. Polyamines have very high concentrations in cells (0.1−30 mM), and their binding to DNA is driven by electrostatic interactions. Polyamines typically bind in the minor groove of DNA. However, because of the unusual structure of iMs, it was unknown whether polyamines might also bind and stabilize iMs. The study described here was undertaken to analyze polyamine−iM interactions. The thermal stability and pH dependence of iM structures were determined in the presence of polyamines. In contrast to dsDNA, our results suggest that polyamines have considerably weaker interactions with iMs, as demonstrated by the minimal change in iM pH dependence and thermal stability. Our results suggest that polyamines are unlikely to provide a significant source of iM stabilization in vivo
Effects of Polyamine Binding on the Stability of DNA i‑Motif Structures
B-form
DNA can adopt alternative structures under conditions such
as superhelical duress. Alternative DNA structures are favored when
there is asymmetric distribution of guanosine and cytosine on complimentary
DNA strands. A guanosine-rich strand can form a four-stranded structure
known as a quadruplex (G4). The complimentary cytosine-rich strand
can utilize intercalating cytosine–cytosine base pairing to
form a four-stranded structure known as the i-motif (iM). Both secondary
structures are energetically uphill from double-strand DNA (dsDNA),
meaning that additional factors are needed for their formation. Most
iMs require slightly acidic conditions for structure stabilization.
However, crowding agents such as polyethylene glycols and dextrans
can shift the pKa of the iM to near-physiological
pH ≈ 7. Nucleic acids have long been known to be bound and
stabilized by polyamines such as putrescine, spermidine, and spermine.
Polyamines have very high concentrations in cells (0.1–30 mM),
and their binding to DNA is driven by electrostatic interactions.
Polyamines typically bind in the minor groove of DNA. However, because
of the unusual structure of iMs, it was unknown whether polyamines
might also bind and stabilize iMs. The study described here was undertaken
to analyze polyamine–iM interactions. The thermal stability
and pH dependence of iM structures were determined in the presence
of polyamines. In contrast to dsDNA, our results suggest that polyamines
have considerably weaker interactions with iMs, as demonstrated by
the minimal change in iM pH dependence and thermal stability. Our
results suggest that polyamines are unlikely to provide a significant
source of iM stabilization in vivo