Graduation Year

2021

Date of Submission

1-2021

Document Type

Open Access Senior Thesis

Degree Name

Bachelor of Arts

Department

W.M. Keck Science Department

Second Department

Biochemistry

Reader 1

Kyle Jay

Reader 2

Ethan Van Arnam

Reader 3

Karl Haushalter

Terms of Use & License Information

Terms of Use for work posted in Scholarship@Claremont.

Abstract

Oxidative damage to the genome can form 8-oxoguanine (oxoG), a premutagenic lesion suggested to play an epigenetic role in the regulation of various cellular pathways. Alongside oxoG in this regulation is the 8-oxoguanine DNA glycosylase (OGG1), which primarily functions to repair oxoG damage via base excision repair, but is also implicated in recruiting NFκB and impacting gene expression associated with cancer growth. This proposal aims to build genome-wide maps of oxoG occupancy, and indirectly OGG1 localization, in healthy lung cells and in non-small cell lung cancer adenocarcinoma cells in order to identify regulatory regions in the genome at which oxoG is prevalent at higher rates in cancer cells relative to healthy cells. Measuring the occupancy of oxoG will be accomplished using two relatively new methods known as OG-seq and enTRAP-seq, both of which improved upon the resolution, throughput, and the scope of previous mapping techniques. The transcriptional changes resulting from increased oxoG/OGG1 occupancy will be quantified using Real Time qRT-PCR. The results of these experiments will aid in characterizing the roles of oxoG and OGG1 in regulation of transcription associated with cancer growth and can inform effective oncological therapeutic development.

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