NIH R01 · 2025
Role of DNA structural dynamics in mutagenesis and oncogenesis
Project Summary Mutations are fundamental to evolution, yet they can also cause cancer and various genetic disorders. Despite their significance, our understanding of processes which generate or defend against mutations is incomplete. We don’t understand why the probability of a base substitution mutation varies by many orders of magnitude depending on the type of substitution and sequence context or why the efficiency of DNA damage repair differs significantly depending on the kind of damage and sequence. Neither the sequence of the DNA nor its three- dimensional structure can explain most mutational signatures and the biochemical origins of most signatures remain unknown. The central…
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