Characterize change in carcinogen susceptibility in loss of RB1 mutants
Abstract/Contents
- Abstract
- The distribution of initial DNA damage acquisition, repair rate and distribution of mutation are strongly influenced by global and local chromatin structure of the genome. Specifically, heterochromatic regions of the genome tend to acquire more DNA damage, repair slower and accumulate more mutations. However, whether losing functions of a chromatin modifier could alter carcinogen susceptibility remains unknown. We generated a CRISPR knock out mutant of RB1 (RB1KO), a known tumor suppressor that regulates heterochromatin structure in the genome. Comparative analysis of the genome wide map of UV damage in RB1KO and wild type reveals both local and global changes of carcinogen susceptibility in RB1KO. For instance, closed domain, as well as pericentric and subtelomeric regions of the genome become more susceptible in RB1KO. More importantly, some cancer driver genes, such as telomerase reverse transcriptase(TERT), becomes more susceptible to UV. Overall, our study demonstrates for the first time that the disruption of a tumor suppressor can alter global carcinogen susceptibility, potentially influencing mutation distributions. We established that the maintenance of proper global genome architecture and regional chromatin structure can potentially regulate DNA damage acquisition upon carcinogen exposure.
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 | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Wong, Ka Man |
|---|---|
| Degree supervisor | Morrison, Ashby J |
| Thesis advisor | Morrison, Ashby J |
| Thesis advisor | Dixon, Scott James, 1977- |
| Thesis advisor | Fraser, Hunter B |
| Thesis advisor | van Rechem, Capucine |
| Degree committee member | Dixon, Scott James, 1977- |
| Degree committee member | Fraser, Hunter B |
| Degree committee member | van Rechem, Capucine |
| Associated with | Stanford University, Department of Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Ka Man Wong. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/zx395rw2805 |
Access conditions
- Copyright
- © 2021 by Ka Man Wong
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