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Barrett Powell '18, Chemistry

Investigating Non-canonical DNA Structures as Anti-Cancer Drug Targets

As cells divide, certain DNA sequences in their genomes are intrinsically harder to replicate than others, which can lead to cancer-causing mutations. Bioinformatic studies of the mammalian genome identified a variety of such sequences; my thesis focuses on one: (CAGAGG)n repeats. We suggest that (CAGAGG)n folds into an unknown structure that does not fall into any currently known category of DNA motifs. We hypothesize the structure forms stacked planar G-C-G-C tetrads connected by AGAG loops in an overall antiparallel conformation. My thesis has focused on verifying this model through direct measures (x-ray crystallography) and indirect measures (cause-and-effect structural modifications).