Abstract

Called “the guardian of the genome,” p53 is one of the most studied proteins associated with cancer. After activation, p53 induces its target genes with different kinetics, i.e., early induction or delayed induction. However, this difference in kinetics of gene induction has not been examined genome-wide. This study uses RNA-seq time course data (0-hour, 6-hour, 12-hour and 24-hour) via drug induction with 5-fluorouracil (5-FU), and compares that data to previously published ChIP-seq data. We found that, while there is an induction of a number of genes at 6 hours, there appears to be a delayed phase of induction occurring at 24 hours, including some of the genes that have been upregulated previously, such as CDKN1A and BBC3. Combining published ChIP-seq data, we are able to narrow our dataset to a select group of genes of particular interest, which are associated with known p53 functions such as apoptosis and cell cycle arrest. We propose that the early phase of induction is due to existing p53 proteins in cells, while the delayed phase of induction is probably due to accumulation of the p53 protein and lack of degradation of p53 protein, which is likely related to its interactions with MDMX and MDM2.

Publication Date

5-19-2017

Document Type

Thesis

Student Type

Graduate

Degree Name

Bioinformatics (MS)

Department, Program, or Center

Thomas H. Gosnell School of Life Sciences (COS)

Advisor

Feng Cui

Advisor/Committee Member

Andre Hudson

Advisor/Committee Member

Gary R. Skuse

Campus

RIT – Main Campus

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