Adventures with Four-Stranded DNA structures

Dr Zoe Waller, University of East Anglia. Part of the chemistry organic seminar series.



DNA can adopt many different conformations and amongst the best-studied are G-quadruplexes, four-stranded secondary structures formed from sequences rich in guanine.1 The regions of DNA which form in the cytosine-rich sequences opposite G-quadruplexes are also able to form i-motifs, also four stranded structures comprised of parallel-stranded DNA duplexes connected in an anti-parallel orientation by intercalated, cytosine–cytosine base pairs.2 i-Motifs are stabilised by acidic conditions, which promote C-C base pairing via hemi-protonation of the N3; folding is rapid and this property has been utilised in many different nanotechnological applications. It is often assumed that i-motif formation is dependent on low pH, but there have always been examples where they are still present under neutral conditions.3 There are also now cases where i-motif can form at neutral and slightly alkaline pH depending on the types of sequence,4,5 conditions6-8 and the presence of ligands.9 Moreover, there are examples of stabilisation of i-motif structures resulting in disruption of telomerase10 and enhancement of gene expression.11

Here we describe work in our group towards the stabilisation of four-stranded DNA structures and their applications in nanotechnology and biology.



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