title: 4n-1 Is a "Sweet Spot" in DNA i-Motif Folding of 2'-Deoxycytidine Homopolymers.
abstract: Strands of DNA with four or more contiguous runs of 2'-deoxycytidine (dC) nucleotides have the potential to adopt i-motif folds, generally under mildly acidic conditions. Analysis of dC homo-oligonucleotide strands ranging in length from 10 to 30 nucleotides by five different pH-dependent methods identified a pattern in strand length vs stability. Beginning with dC11, which does not fold, the transition pH (pHT) increased with chain length with the addition of up to four nucleotides, after which the stability dramatically decreased, and the trend repeated this cycle up to dC27. The analysis found dCnstrands of length 15, 19, 23, and 27 nucleotides (i.e., 4n-1) to have pHTvalues >7.2 and thermal stabilities >37 °C at pH 7.0. Model studies using thymidine nucleotides to lock in i-motif loop lengths support the conclusion that the most stable dCni-motifs possess one nucleotide in each of the three loops and a core built of an even number of base pairs. The pattern identified from the model studies occurs with a frequency of four nucleotides at lengths of 15, 19, 23, and 27 in accordance with the results obtained for the dCnstrands. This observation led us to interrogate the human genome for dCnruns. Inspection of the human genome indicates that dCnruns are enriched in critical regions of the genome (promoters, UTRs, and introns), while being depleted in coding and intergenic regions, and these findings may have biological implications. Lastly, the ability to tune i-motif stabilities by the length of the strand might be harnessed for stimulus-responsive applications in DNA scaffolds, sensors, nanotechnology, and other chemical applications.
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Aaron M
authors.identifier: 0000-0002-2000-0310
authors.initials: AM
authors.lastname: Fleming
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Yun
authors.identifier: 0000-0002-6624-0934
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: R Aaron
authors.initials: RA
authors.lastname: Rogers
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Judy
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Ashlee D
authors.initials: AD
authors.lastname: Burton
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Connor B
authors.initials: CB
authors.lastname: Carlisle
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Cynthia J
authors.identifier: 0000-0001-7253-8529
authors.initials: CJ
authors.lastname: Burrows
mesh_terms: D004247:DNA / Q000737:chemistry*; D003841:Deoxycytidine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D059372:Nucleotide Motifs; D011108:Polymers / Q000737:chemistry*
chemical_list: D011108:Polymers; D003841:Deoxycytidine; D004247:DNA