Dr. Alessandra PICCHIOTTI
Hamburg Advanced Research Centre for Bioorganic Chemistry (HARBOR) Hamburg University (Germany)
Biomolecular Sciences and Biotechnology Institute GBB, Biochemistry department, University of Groningen (the Netherlands)
Abstract
Reactive oxygen species (ROS) play a central role in cellular oxidative stress, driving DNA damage that compromises genomic stability, tightly linked to carcinogenesis. Paradoxically, the same oxidative pathways are exploited in cancer therapy. Yet, despite its biological and clinical relevance, the molecular mechanism of ROS–DNA interaction remains only partially understood, largely because the key events occur on ultrafast femtosecond timescales beyond the reach of conventional biophysical techniques, such as HPLC, Comet Assay, Immunofluorescence Imaging or PCR. These limitations prevent the study of the earliest structural changes from ROS-DNA interaction, while they happen.
In this talk, I will present an integrated experimental platform combining femtosecond time-resolved spectroscopy with quasi–single-particle DNA spectroscopy to resolve, in real time, the dynamics of oxidative damage initiation. We focus on how ROS-induced lesions disrupt π-stacking interactions, destabilize base pairing, and produce transient conformational DNA structures.
Together, these methodologies open a new window into the ultrafast physics of DNA oxidation, providing mechanistic insight directly relevant to understanding cancer initiation and optimizing ROS-based therapeutic strategies.
