Ultraviolet light-induced genome instabilities
Abstract/Contents
- Abstract
- Exposure to the ultraviolet (UV) radiation in sunlight creates DNA lesions, which if left unrepaired can induce mutations and contribute to skin cancer. The two most common UV-induced DNA lesions are the cis-syn cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts (6-4PP), both of which can initiate mutations. Interestingly, mutation frequency across the genomes of many cancers is heterogenous with significant increases in heterochromatin. Corresponding increases in UV lesion susceptibility and decreases in repair are observed in heterochromatin versus euchromatin. However, the individual contributions of CPDs and 6-4PPs has not been systematically examined in specific genomic and epigenomic regions. In this study, we generated a genome-wide map of 6-4PP lesion abundance in primary cells and conducted a comprehensive analysis to determine the genetic and epigenetic features associated with 6-4PP susceptibility. We found high degree of similarity between 6-4PP and CPD formation, with enrichment of both in heterochromatin regions. However, when examining the relative levels of the two UV lesions, we found that bivalent and Polycomb repressed chromatin states were uniquely more susceptible to 6-4PPs. Interestingly, when comparing UV susceptibility and repair with melanoma mutation frequency in these regions, disparate patterns were observed in that susceptibility was not always inversely associated with repair and mutation frequency. Functional enrichment analysis hint at mechanisms of negative selection for these regions that are essential for cell viability and immune function and induce cell death when mutated. Ultimately, these results reveal both the similarities and differences between UV-induced lesions that contribute to skin carcinogenesis
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Perez, Brian Steven |
|---|---|
| Degree supervisor | Morrison, Ashby J |
| Thesis advisor | Morrison, Ashby J |
| Thesis advisor | Dixon, Scott James, 1977- |
| Thesis advisor | Gozani, Or Pinchas |
| Thesis advisor | Sage, Julien |
| Degree committee member | Dixon, Scott James, 1977- |
| Degree committee member | Gozani, Or Pinchas |
| Degree committee member | Sage, Julien |
| Associated with | Stanford University, Department of Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Brian Steven Perez |
|---|---|
| Note | Submitted to the Department of Biology |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Brian Steven Perez
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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