Thesis
Examining the Roles of RAD51 Paralogs in Protecting Against APOBEC Mutagenesis in Human Cancer Cells Facilitated By CAS9-Mediated Duplex Sequencing
Washington State University
Master of Science (MS), Washington State University
2022
DOI:
https://doi.org/10.7273/000005208
Abstract
Understanding the process of DNA damage and mutation accumulation is essential to understanding the origins of tumorigenesis. How DNA damage is induced and repaired or tolerated can drastically impact the mutation load, progression, and severity of cancer. APOBEC3A is a prominent cytidine deaminase enzyme that has been implicated in the mutagenesis of many cancers. APOBEC3A is part of a larger cytidine deaminase family that can edit DNA and restrict viruses through DNA damage. The dysregulated function of APOBEC3A can lead to mutation accumulation and tumorigenesis in human cells. APOBEC3A-induced DNA damage has been suggested to occur most frequently during replication in the replication fork where it has access to its preferred ssDNA substrate. It is currently not known exactly how human cells respond to APOBEC-induced ssDNA damage during replication and if error-free lesion bypass mediated by homologous recombination (HR) repair is a means to reduce APOBEC-induced mutation. Here, we attempt to elucidate the extent to which HR repair is utilized to limit APOBEC-induced damage, and what players of the HR pathway are most prominent. In conjunction with this goal, we also test a novel method, Cas9-mediated duplex sequencing, to aid in the identification of mutations from populations of human cancer cells.
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Details
- Title
- Examining the Roles of RAD51 Paralogs in Protecting Against APOBEC Mutagenesis in Human Cancer Cells Facilitated By CAS9-Mediated Duplex Sequencing
- Creators
- Nicholas Samuel Bray
- Contributors
- Steven A Roberts (Advisor)John M Hinz (Committee Member)Eric A Shelden (Committee Member)John J Wyrick (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Molecular Biosciences, School of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Number of pages
- 74
- Identifiers
- 99901019841101842
- Language
- English
- Resource Type
- Thesis