Metallation‐induced heterogeneous dynamics of DNA revealed by single‐molecule FRET

Berrocal-Martin, R., Sanchez-Cano, C., Chiu, C. K.C., Needham, R. J., Sadler, P. J. and Magennis, S. W. (2020) Metallation‐induced heterogeneous dynamics of DNA revealed by single‐molecule FRET. Chemistry: A European Journal, 26(22), pp. 4980-4987. (doi: 10.1002/chem.202000458) (PMID:31999015)

Abstract

The metallation of nucleic acids is key to wide‐ranging applications, from anticancer medicine to nanomaterials, yet there is a lack of understanding of the molecular‐level effects of metallation. Here, we apply single‐molecule fluorescence methods to study the reaction of an organo‐osmium anticancer complex and DNA. Individual metallated DNA hairpins are characterized using Förster resonance energy transfer (FRET). Although ensemble measurements suggest a simple two‐state system, single‐molecule experiments reveal an underlying heterogeneity in the oligonucleotide dynamics, attributable to different degrees of metallation of the GC‐rich hairpin stem. Metallated hairpins display fast two‐state transitions with a two‐fold increase in the opening rate to ~2 s‐1, relative to the unmodified hairpin, and relatively static conformations with long‐lived open (and closed) states of 5 s to ≥ 50 s. These studies show that a single‐molecule approach can provides new insight into metallation‐induced changes in DNA structure and dynamics.

• Item Type: Articles
• Additional Information: The authors thank the EPSRC (PhD studentships for RBM and CKCC, Grant no. EP/P030572/1), CRUK/EPSRC (Grant No. C53561/A19933), The Wellcome Trust (Grant No. 107691/Z/15/Z), and AngloAmerican for support.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Magennis, Dr Steven and Berrocal Martin, Mr Raul
• Authors: Berrocal-Martin, R., Sanchez-Cano, C., Chiu, C. K.C., Needham, R. J., Sadler, P. J., and Magennis, S. W.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Chemistry: A European Journal
• Publisher: Wiley
• ISSN: 0947-6539
• ISSN (Online): 1521-3765
• Published Online: 30 January 2020
• Copyright Holders: Copyright © 2020 Wiley-VCH Verlag GmbH and Co. KGaA
• First Published: First published in Chemistry: A European Journal 26(22): 4980-4987
• Publisher Policy: Reproduced in accordance with the publisher copyright policy