Understanding the rules of life

Bioscience for an integrated understanding of health

Category: Standard Studentships

Understanding the genesis of chromosomal breakpoints: the role of a virus indriving MYC translocations in B cells

Project No. 2476


Primary Supervisor

Prof Michelle West – University of Sussex


Dr Tim Fenton- University of Southampton



Epstein-Barr virus (EBV) reprogrammes B cells by usurping the signalling pathways and transcriptional networks that control cell growth and survival.

This gives rise to an immortal cell in which the virus can persist. This growth transforming property of EBV is important in the development of Burkitt’s lymphoma (BL), but BL cells also contain a translocation of the MYC oncogene.This results in high-level MYC expression which contributes to deregulated B cell growth. A long-standing question concerns the role of EBV in the genesis of the MYC breakpoint; does the virus cause it or does the virus expand a pool of cells in which it already exists? Our work provided evidence that the MYC breakpoint in EBV-positive BL occurs at upstream enhancers that are activated by the binding of a key EBV transcription factor (EBNA2). Activation-induced cytidine deaminase (AID) levels are also induced by EBV and off-target AID activity is known to cause breakpoints and to home in on active enhancers. This project will test the hypothesis that EBV EBNA2 activation of MYC enhancers makes them susceptible to the AID-induced double-strand breaks that lead to chromosomal translocations. Aims: 1. Map MYC translocations in EBV-positive BL cell lines and BL samples (obtained from US collaborators) using long-read sequencing. This will allow us to obtain accurate information on breakpoint locations. 2. Induce AID expression -/+ EBNA2 in an EBV-infected cell line and map the location of abasic sites (formed as result of DNA damage) using snAP-seq (a chemical approach that allows mapping of these sites at single-nucleotide resolution). This will allow us to determine the role of EBNA2 in directing AID activity genome-wide. This work will provide important information on the fundamental mechanisms involved in DNA damage and transcription and aid our understanding of genetic events in oncogenesis