Mechanism of TOP1-dependent mutations in human cancer
Lopez, Vanessa
Lopez, Vanessa
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Abstract
Cancer cells typically have elevated rates of mutation, which promotes metastasis, cancer progression, and therapeutic resistance. TOP1 acts to remove DNA supercoiling during transcription, which creates DNA-protein intermediates called TOP1 cleavage complexes that contribute to transcription-associated mutagenesis (TAM) and produces a signature of 2-to-5bp deletions. However, we identified additional TOP1-induced signatures whose mechanism's contribution to tumorigenesis are unknown. We aim to characterize the TOP1-induced TAM and determine its role in human cancer mutagenesis by measuring mutation rates and producing mutation spectra in a U2OS-derived mutation reporter cell line and whole-genome sequencing.
Description
Undergraduate
Date
2025-06-02