this is the sole function of ARID1A in tumourigenesis.
In addition to regulating gene expression, ARID1A maintains genome stability through roles in replication stress responses, centromere structure and function, and DNA repair. For example, we recently found that ARID1A helps stablise repair proteins at damaged DNA (Simões-Sousa et al., 2025). While the impact of ARID1A loss on pathways that maintain genome stability is well established, the mechanisms that underpin these roles are not yet fully clear.
Using cutting-edge long read sequencing approaches, we recently established that loss of ARID1A has an unexpected impact on the pattern of chromatin organisation in cells – separate from the expected changes at gene enhancers – that impacts on nucleosome occupancy and positioning. In this project, we will explore this newly identified aspect of ARID1A function to establish how it creates these patterns in chromatin fibers, determine what cellular functions this normally provides, and how cells cope when ARID1A is unable to do this. Finally, we will investigate whether and how this contributes to the role of ARID1A as a tumour suppressor.
Candidates must have, or be on track to receive, a First- or Upper Second- class Honours degree (or a Masters) in molecular biology or a closely related area and have experience in experimental lab work, and must have a basic knowledge of chromatin biology, epigenetics, and genomics.
References
HARROD, A., LANE, K. A. & DOWNS, J. A. 2020. The role of the SWI/SNF chromatin remodelling complex in the response to DNA double strand breaks. DNA Repair (Amst), 93, 102919.
SIMÕES-SOUSA, S., AMIN, N., LANE, K. A., HARROD, A., PEDERSEN, M., PARDO, M., RASETTI-ESCARGUEIL, C., KOZIK, Z., BEGG, K. A. G., RIBEIRO, A., BANERJEE, S., STUCKI, M., HARRINGTON, K. J., CHOUDHARY, J. S. & DOWNS, J. A. 2025. ARID1A stabilises non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin. bioRxiv, 2025.05.10.653238.
