2′-Fluoroarabinonucleic acid modification traps G-quadruplex and i-motif structures in human telomeric DNA
2´-Fluoroarabino modifications slow down the interconversion kinetics between different DNA structures in telomeric sequences.
Abou Assi H, El-Khoury R, González C, Damha MJ.
Nucleic Acids Res 2017 Nov; 45: 11535.
Human telomeres and promoter regions of genes fulfill a significant role in cellular aging and cancer. These regions comprise of guanine and cytosine-rich repeats, which under certain conditions can fold into G-quadruplex (G4) and i-motif structures, respectively. Herein, we use UV, circular dichroism and NMR spectroscopy to study several human telomeric sequences and demonstrate that G4/i-motif-duplex interconversion kinetics are slowed down dramatically by 2′-beta-fluorination and the presence of G4/i-motif-duplex junctions. NMR-monitored kinetic experiments on 1:1 mixtures of native and modified C- and G-rich human telomeric sequences reveal that strand hybridization kinetics are controlled by G4 or i-motif unfolding. Furthermore, we provide NMR evidence for the formation of a hybrid complex containing G4 and i-motif structures proximal to a duplex DNA segment at neutral pH. While the presence of i-motif and G4 folds may be mutually exclusive in promoter genome sequences, our results suggest that they may co-exist transiently as intermediates in telomeric sequences.
PubMed: 29036537. Doi: 10.1093/nar/gkx838. free PMC article
