Speaker
Description
DNA's flexible structure and mechanics are intrinsically linked to its function. Damage to DNA disrupts essential processes, increasing cancer risk. However, it can be exploited in cancer therapeutics by targeting the DNA in cancer cells. The relationship between DNA damage and its mechanics is not well understood. New-generation metallodrugs offer a promising route for anticancer therapies - this study examines two such drugs: Triplatin, which compacts DNA, preventing transcription, and Copper-Oda, which generates reactive oxygen species that damage the DNA.
Using Atomic Force Microscopy, we detect and localise DNA damage caused by these drugs on single molecules with submolecular resolution. We employ our open-source analysis programme, TopoStats, to quantify these damage processes and relate them to DNA mechanics. For Triplatin, we quantify drug-driven DNA compaction and aggregation. For Cu-Oda, we observe single and double-stranded DNA breaks enhanced by a reducing agent found at higher levels in cancer cells.
Understanding metallodrug-driven DNA damage is vital for the further development of new, more targeted cancer therapeutics. Our methodology utilises an open-source image analysis pipeline to probe and quantify various drug-driven DNA conformational changes.
| Authors | Thomas Catley*, Sylvia Whittle, Raphael de Paiva, Andrew Kellett, Alice Pyne |
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| Keywords | Single Molecule Imaging, AFM, Biophysics |
