Transformation of XPV Cells by E6 and E7 Genes of HPV Sensitizes the Cells to UVB Light: Synthetic Lethality and Perspectives to the Treatment of Cervical Cancer
ISEF · 2014 Computational Biology and Bioinformatics
Overview
The human syndrome Xeroderma Pigmentosum (XP) is a rare genetic disease characterized by high sensitivity to sunlight, and, in some cases, early aging and neurodegeneration. Defects on eight different genes are responsible for this disease, and they encode for proteins involved in DNA damage processing, either a lack of Nucleotide Excision Repair (NER) (XP-A to XP-G genes) or a deficiency to encode a DNA polymerase known as XPV variant (XPV or Pol eta) with a normal NER. As a consequence, the cells from these patients are sensitive to UV light, culminating in genomic instability and predisposition to skin cancer. This project aims to evaluate the responses of cellular cultures of fibroblasts from XPV patients (mutated in the XPV gene) to the UVB light after the transformation by E6 and E7 genes of HPV-16 virus. These two proteins (E6 and E7) degrade p53 and pRb proteins respectively, which play essential roles in DNA damage responses and cell cycle regulation. To test cell sensitivity, I performed XTT assay (cellular viability) and flow cytometry. The results confirm that transformation highly sensitized the cells to UVB light, mostly due to increased apoptosis induction. This indicated clearly that the impairment of the two regulator proteins (P53 and pRb) and the Pol eta, simultaneously, can lead to a synthetic lethality situation, where at least two pathways are blocked, resulting in cell death in situation of DNA damage. Therefore, I propose that inhibiting or silencing the XPV gene can sensitize tumor cells from cervical cancer, caused basically due to HPV transformation to DNA damaging chemotherapeutic agents. This would offer a strong tool to battle this type of cancer.
Competition history
- ISEF 2014
Resources
Related projects
ISEF · 2016
The Effects of Expressing DNA Repair Enzymes, UVDE and cv-pdg, in E. coli cells under UVB Light
ISEF · 2017
Rescue of Nucleotide DNA Repair Deficiencies to UVB and Solar-Simulated Irradiation by Pyrimidine Dimer Glycosylases and UV Endonucleases
ISEF · 2017
Identifying Natural Compounds and Genes that Will Protect from UV Radiation
ISEF · 2018
A Novel Approach to a p53-Stabilizing Agent to Accelerate Cell Apoptosis and Initiate Cell Arrest and Curb Malignancy of Tumor Cells
Closest projects by meaning, across every fair and year in the corpus.
Source: Regeneron International Science and Engineering Fair