Regulation of cell homeostasis in response to DNA damage in Breast Cancer cell lines with different p53 status

Project: Research

Project Details

Description

The goal of this project is to identify direct p53 target genes in breast cancer cell lines with different p53 status and follow their expression in response to DNA damage by RNAseq. The transcription factor p53 is a fundamental regulator of DNA repair, cell cycle progression and cell death, thereby ensuring genome integrity and stability. We are using three breast cancer cell lines: MCF-7 that has wild type p53 and MDA-MB231 and T47D that have mutations in the DNA-Binding Domain (DBD) of p53. However, the mutations affect different amino acid (MDA-MB231 R280K, while T47D has L194F) within the DBD such that the former is in a critical region and therefore predicted to have a strong effect on p53 functionality while the latter is in a permissive region much more tolerant to changes, predicted to have a minor effect.
The genes directly regulated by p53 were identified using a combination of informatic resources available: ChIP atlas detects genome-wide p53 binding and DoRoThea contains manually curated lists of genes regulated by p53. The target genes are mapped to cellular pathways using Reactome and their expression in the cell lines is assessed by RNAseq. We use 4NQO to induce double strand DNA breaks and follow the response in terms of cell behaviour using flow cytometry and imaging and gene regulation with RNAseq.

Layman's description

This project is being performed and developed with the participation of final year students: Patricia Eror Barnes and Maria Jose de la Concha Escobedo, and second year summer student Charming Pena.
StatusActive
Effective start/end date1/05/24 → …

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