Mechanism of TOP1-dependent mutations in human cancer
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.
Primary Faculty Mentor Name
Elise Lauterbur
Status
Undergraduate
Student College
College of Agriculture and Life Sciences
Program/Major
Biology
Primary Research Category
Life Sciences
Mechanism of TOP1-dependent mutations in human cancer
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.
