Two Opposing Effects of Monovalent Cations on the Stability of i-Motif Structure
Sung Eun Kim1, Seok-Cheol Hong1
1Center for Molecular Spectroscopy and Dynamics, Institute for Basic Science, Seoul, Korea, Department of Physics, Korea University, Seoul 02841, Korea.
Insights
Monovalent cations impact DNA i-motif (iM) stability through opposing forces. Increased cation concentration destabilizes iM structure, with lithium ions showing the strongest effect.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural DNA Biology
Background:
- Cytosine-rich single-stranded DNA forms i-motif (iM) structures at acidic pH.
- Previous studies on monovalent cation effects on iM stability lack consensus.
- Understanding iM stability is crucial for its potential applications.
Purpose of the Study:
- To investigate the influence of monovalent cations on iM structure stability.
- To elucidate the ambivalent role of cations in iM formation.
- To determine the balance between electrostatic screening and base pair disruption.
Main Methods:
- Utilized fluorescence resonance energy transfer (FRET)-based analysis.
- Examined three distinct iM structures derived from human telomere sequences.
- Assessed the impact of varying concentrations of Li+, Na+, and K+.
Main Results:
- Monovalent cations destabilize the protonated cytosine-cytosine (C:C+) base pair in iM structures.
- Lithium ions (Li+) exhibited the greatest destabilizing effect.
- Monovalent cations, particularly Li+, increase single-stranded DNA flexibility, aiding iM formation.
Conclusions:
- iM stability is governed by a delicate balance between cation-mediated electrostatic screening and disruption of cytosine base pairing.
- Monovalent cations exert both stabilizing (via screening) and destabilizing (via disruption) effects on iM.
- Lithium ions play a significant role in modulating iM structure dynamics.
Abstract:
At acidic pH, cytosine-rich single-stranded DNA can be folded into a tetraplex structure called i-motif (iM). In recent studies, the effect of monovalent cations on the stability of iM structure has been addressed, but a consensus about the issue has not been reached yet. Thus, we investigated the effects of various factors on the stability of iM structure using fluorescence resonance energy transfer (FRET)-based analysis for three types of iM derived from human telomere sequences. We confirmed that the protonated cytosine-cytosine (C:C+) base pair is destabilized as the concentration of monovalent cations (Li+, Na+, K+) increases and that Li+ has the greatest tendency of destabilization. Intriguingly, monovalent cations would play an ambivalent role in iM formation by making single-stranded DNA flexible and pliant for an iM structure. In particular, we found that Li+ has a notably greater flexibilizing effect than Na+ and K+. All taken together, we conclude that the stability of iM structure is controlled by the subtle balance of the two counteractive effects of monovalent cations: electrostatic screening and disruption of cytosine base pairing.
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