Accurate genome duplication is essential for all forms of life. The molecular machinery that orchestrates this process is collectively termed the replisome. Replisomes are complex arrangements of molecular machines that co-ordinate DNA template unwinding, DNA synthesis, histone transfer and other replication-coupled processes including a variety of DNA repair mechanisms. Our laboratory primarily uses a combination of biochemical reconstitution and structural biology to examine replisome structure, function and mechanism. We have recently reconstituted a functional human replisome from purified proteins for the first time and have determined the structure of this complex by electron-cryomicroscopy (cryo-EM). Over the coming years, we will use this ground-breaking approach to investigate the structural and mechanistic basis of human replication fork progression, both during unperturbed DNA replication and when the replisome encounters obstacles such as DNA damage and protein barriers.
We are looking for an ambitious and enthusiastic student to join our research group to undertake a project addressing a key aspect of human replisome function. You will gain extensive experience in protein purification, complex biochemical reconstitution and structural biology, particularly cryo-EM. Our focused research group provides an excellent environment to learn new techniques whilst working on an independent research project.
References
Baris, Y., Taylor M.R.G., Aria, V. and Yeeles, J.T.P. (2022).
Fast and efficient DNA replication with purified human proteins.
Nature. 10.1038/s41586-022-04759-1.
Jenkyn-Bedford, M., Jones, M.L., Baris, Y., Labib, K.P.M., Cannone, G., Yeeles, J.T.P., and Deegan, T.D. (2021).
A Conserved Mechanism for Regulating Replisome Disassembly in Eukaryotes.
Nature. 10.1038/s41586-021-04145-3.
Jones, M.L., Baris, Y., Taylor, M.R.G., and Yeeles, J.T.P. (2021).
Structure of a human replisome shows the organisation and interactions of a DNA replication machine.
The EMBO Journal, e108819.