Circadian rhythm is a ~24-h mechanism that keeps our physiology and behavior in synchrony with environmental changes. PERIOD2 (PER2) is a core component of the circadian clock and a candidate tumor suppressor as its knockout expression results in a cancer-prone animal. p53 is an effector in the DNA damage response and regulates downstream effectors by trans-activation. Recent studies in our lab show that PER2 can bind to p53, and regulates the trans-activation function. This project studied the subcellular distribution of PER2 in response to DNA damage, and explored the role of p53 in the regulation of PER2 subcellular distribution. We found that PER2 accumulates in the nucleus in response to DNA damage, and such accumulation is independent of p53. In addition, we analyzed Single Nucleotide Polymorphisms (SNP) of PER2 in the 1000 Genome project to gain insight onto how missense mutations in PER2 lay at the interface of p53:PER2 binding. In a separate project, we also performed bioinformatics analysis on the iron related genes to discuss the circadian regulation of iron genes in the liver. These findings shed light on the regulation of PER2 under genotoxic stress, genetic variations of Per2 in normal human population, and expression of circadian genes under iron controlled diets. / Master of Science / Circadian rhythm is a ~24-h mechanism that keeps the body in synchrony with the environment. Period2 (Per2) is a gene at the core of circadian rhythm in mammals. In this work, we found that PER2 accumulates in the nucleus of cells in response to DNA damage. In addition, we analyzed the genetic variation of PER2 in general human population to gain insight onto how mutations in PER2 affect the risk of cancer that’s associated to circadian disruption. In a separate project, we performed bioinformatics analysis on the genes related to iron metabolism, and showed pattern of circadian regulation of iron genes in the liver. These findings shed light on how circadian rhythm responds to genotoxic stress, and summarized genetic variations of Per2 in normal human population, and the expression of circadian genes under iron-controlled diets.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/100865 |
| Date | 24 May 2019 |
| Creators | Jiang, Liang |
| Contributors | Biological Sciences, Finkielstein, Carla V., Tyson, John J., Dervisis, Nikolaos G., Kojima, Shihoko |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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