Issue 24, 2018

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

Abstract

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

Supplementary files

Article information

Article type
Paper
Submitted
21 Mai 2018
Accepted
04 Jun 2018
First published
04 Jun 2018

Org. Biomol. Chem., 2018,16, 4537-4546

Author version available

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

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements