Building the human replisomeGroup Leader Page
Accurate genome duplication is essential for all forms of life. The molecular machine that orchestrates this process is the replisome: a complex ensemble of proteins that co-ordinates DNA template unwinding, DNA synthesis, histone transfer and several other replication-coupled processes. Our laboratory uses a combination of biochemical reconstitution and structural biology to examine replisome structure and function. We have recently reconstituted a functional human replisome entirely with purified proteins, starting from the purified CMG replicative helicase, and have determined the structure of this complex by electron-cryomicroscopy (cryo-EM). Over the coming years, this system will enable us to directly investigate how the human replisome navigates chromatinised templates and how it interfaces with DNA repair and recombination pathways that are required to sustain DNA replication under conditions of replication stress. This is important because there are many factors required to maintain replication fork progression in human cells that are absent from budding yeast, which is currently the best characterised model system.
We are looking for an enthusiastic and ambitious student to join our research group. During your PhD you will further develop a reconstituted replication system to investigate how the human replisome collaborates with DNA repair and recombination pathways to sustain replisome progression under stress conditions. You will become an expert in protein purification and complex biochemical reconstitution and will have the opportunity to gain experience in structural biology. Our focused research group provides an excellent environment to learn new techniques whilst working on an independent research project.
Taylor, M.R.G., and Yeeles, J.T.P. (2018).
The Initial Response of a Eukaryotic Replisome to DNA Damage.
Mol Cell 70, 1067-1080 e1012.
Bartetić, D., Jenkyn-Bedford, M., Aria, A., Cannone, G., Skehel, M., Yeeles, J.T.P. (2020)
Cryo-EM structure of the fork protection complex bound to CMG at a replication fork.
Mol Cell 78, 926-940 e13.
Guilliam, T and Yeeles J.T.P. (2020)
Reconstitution of translesion synthesis reveals a mechanism of eukaryotic DNA replication restart.
Nat Struct Mol Biol 27, 450-460.