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Issue 24, 2018
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Unraveling the 4n − 1 rule for DNA i-motif stability: base pairs vs. loop lengths

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Previously our laboratory identified that poly-2′-deoxycytidine (dCn) strands of DNA with lengths greater than 12 nucleotides could adopt i-motif folds, while the pH-dependent stabilities follow a 4n − 1 repeat pattern with respect to chain length (J. Am. Chem. Soc., 2017, 139, 4682–4689). Herein, model i-motif folds in which loop configurations were forced by judiciously mutating dC to non-dC nucleotides allowed a structural model to be proposed to address this phenomenon. The model was developed by systematically studying two i-motifs with either an even or odd number of d(C·C)+ hemiprotonated base pairs in the core. First, a trend in the pH-dependent stability vs. loop nucleotide identity was observed: dC > dT ∼ dU ≫ dA ∼ dG. Next, loops comprised of dT nucleotides in the two different core base pair configurations were studied while systematically changing the loop lengths. We found that an i-motif with an even number of base pairs in the core with a single nucleotide in each of the three loops was the most stable, as well as an i-motif with an odd number of core base pairs having one nucleotide in the two exterior loops and three nucleotides in the central loop. A systematic increase in the central loop from 1–4 nucleotides for an odd number of base pairs in the i-motif core reproduced the 4n − 1 repeat pattern observed in the poly-dCn strands. Additional loop configurations were studied to further support the model. The results are discussed with respect to their biological relevance.

Graphical abstract: Unraveling the 4n − 1 rule for DNA i-motif stability: base pairs vs. loop lengths

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The article was received on 21 May 2018, accepted on 04 Jun 2018 and first published on 04 Jun 2018

Article type: Paper
DOI: 10.1039/C8OB01198B
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Org. Biomol. Chem., 2018,16, 4537-4546

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    Unraveling the 4n − 1 rule for DNA i-motif stability: base pairs vs. loop lengths

    A. M. Fleming, K. M. Stewart, G. M. Eyring, T. E. Ball and C. J. Burrows, Org. Biomol. Chem., 2018, 16, 4537
    DOI: 10.1039/C8OB01198B

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