Or Szekely

Congratulations to Or Szekely, former Zuckerman-CHE Israeli Woman Postdoctoral Scholar, on her recent study, Assessing the contribution of rare DNA states to cancer mutational signatures using sequence-specific conformational fingerprinting, published in Nature Communications.” The study asks why certain cancer-driving mutations depend so strongly on the surrounding DNA sequence.By developing a molecular epidemiology approach that quantifies how frequently rare, short-lived DNA conformations appear in specific sequence contexts and comparing these “conformational fingerprints” with known cancer mutational signatures, her team identified plausible links between DNA’s dynamic structural states and characteristic mutation patterns observed across tumors, helping connect molecular biophysics to real-world cancer genomes.

Abstract:
Rare and short-lived DNA conformations are proposed to be key drivers of mutagenesis, yet assessing their contribution to mutational signatures found in human cancers remains challenging. Here, we develop an approach that quantifies the sequence-dependent propensity to form a rare DNA conformation and compare the resulting fingerprint against cancer mutational signatures.