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DNA structural changes induced by intermolecular triple helix formation

DNA structural changes induced by intermolecular triple helix formation
DNA structural changes induced by intermolecular triple helix formation
DNase I footprints of intermolecular DNA triplexes are often accompanied by enhanced cleavage at the 3′-end of the target site at the triplex–duplex junction. We have systematically studied the sequence dependence of this effect by examining oligonucleotide binding to sites flanked by each base in turn. For complexes with a terminal T.AT triplet, the greatest enhancement is seen with ApC, followed by ApG and ApT, with the weakest enhancement at ApA. Similar DNase I enhancements were observed for a triplex with a terminal C+.GC triplet, though with little difference between the different GpN sites. Enhanced reactivity to diethylpyrocarbonate was observed at As that flank the triplex–duplex junction at AAA or AAC but not AAG or AAT. Fluorescence melting experiments demonstrated that the flanking base affected the stability with a 4 °C difference in Tm between a flanking C and G. Sequences that produced the strongest enhancement correlated with those having the lower thermal stability. These results are interpreted in terms of oligonucleotide-induced changes in DNA structure and/or flexibility.
2470-1343
1679-1687
Sayoh, Ibrahim
aaea482c-fbe4-498c-8006-5efa3ac23313
Rusling, David
d08f1f97-f8a9-4980-a025-ae41c23a938f
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Fox, Keith
9da5debc-4e45-473e-ab8c-550d1104659f
Sayoh, Ibrahim
aaea482c-fbe4-498c-8006-5efa3ac23313
Rusling, David
d08f1f97-f8a9-4980-a025-ae41c23a938f
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Fox, Keith
9da5debc-4e45-473e-ab8c-550d1104659f

Sayoh, Ibrahim, Rusling, David, Brown, Tom and Fox, Keith (2020) DNA structural changes induced by intermolecular triple helix formation. ACS Omega, 5 (3), 1679-1687. (doi:10.1021/acsomega.9b03776).

Record type: Article

Abstract

DNase I footprints of intermolecular DNA triplexes are often accompanied by enhanced cleavage at the 3′-end of the target site at the triplex–duplex junction. We have systematically studied the sequence dependence of this effect by examining oligonucleotide binding to sites flanked by each base in turn. For complexes with a terminal T.AT triplet, the greatest enhancement is seen with ApC, followed by ApG and ApT, with the weakest enhancement at ApA. Similar DNase I enhancements were observed for a triplex with a terminal C+.GC triplet, though with little difference between the different GpN sites. Enhanced reactivity to diethylpyrocarbonate was observed at As that flank the triplex–duplex junction at AAA or AAC but not AAG or AAT. Fluorescence melting experiments demonstrated that the flanking base affected the stability with a 4 °C difference in Tm between a flanking C and G. Sequences that produced the strongest enhancement correlated with those having the lower thermal stability. These results are interpreted in terms of oligonucleotide-induced changes in DNA structure and/or flexibility.

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Accepted/In Press date: 20 December 2019
Published date: 15 January 2020

Identifiers

Local EPrints ID: 437413
URI: http://eprints.soton.ac.uk/id/eprint/437413
ISSN: 2470-1343
PURE UUID: aca11ba5-081a-47dd-a8fc-ec927cb607b2
ORCID for David Rusling: ORCID iD orcid.org/0000-0002-7442-686X
ORCID for Keith Fox: ORCID iD orcid.org/0000-0002-2925-7315

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Date deposited: 29 Jan 2020 17:34
Last modified: 30 Jan 2020 01:33

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