Overcoming replication stress–defining new mechanism from archaea to human

How cells respond to DNA replication stresses (e.g., DNA replication collapse, stalling or hyper-activity) is critical for their survival, and is a hallmark of cancers. This PhD project investigates molecular mechanisms of an emerging replication stress-recovery pathway that is evolutionarily conserved from archaea to human.

The emerging pathway involves multiple protein-protein interactions and DNA processing events that transcend boundaries between well characterised pathways of stress recovery, including those of translesion synthesis (TLS) and homologous recombination (HR). It is now attracting drug discovery research because of its role in driving resistance to commonly used cancer treatments.

To understand more about these processes, this project will delineate, using biochemistry and genetics, specific protein-protein interactions that have been identified in the last 12 months. This will inform about the mechanism by which this emerging pathway controls TLS and HR in human cells and in archaea.

The project is hosted in two labs within the QMC Medical School at the University of Nottingham, and benefits from collaboration with colleagues in Chemistry at Nottingham, and Oncology at Oxford.

While contributing to understanding of new biology through gaining a PhD, the successful applicant will be trained in many techniques that are used to understand molecular biology by protein biochemistry, structural biology, biophysics, and genetic analyses.