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. This is a hugely exciting time DNA for replication research thanks to recent advances in replisome reconstitution reconstitution, structure determination by cryo-EM and DNA sequencing approaches.

Our laboratory primarily uses a combination of biochemical reconstitution, functional DNA replication assays and structural biology to examine replisome structure, function and mechanism. We have recently reconstituted functional human replisomes from purified proteins for the first time and have determined several human replisome structures by 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

Roske, J.J., Yeeles, J.T.P. (2024)
Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand polymerase Pol ε.
Nature Structural and Molecular Biology. 10.1038/s41594-024-01370-y.

Jones, M.L., Aria, V., Baris, Y., Yeeles, J.T.P. (2023)
How Pol α-primase is targeted to replisomes to prime eukaryotic DNA replication
Mol Cell 83(16): 2911-2924

Baris, Y., Taylor, M.R.G., Aria, V., Yeeles, J.T.P. (2022)
Fast and efficient DNA replication with purified human proteins
Nature 606(7912): 204-210

Jenkyn-Bedford, M., Jones, M.L., Baris, Y., Labib, K.P.M., Cannone, G., Yeeles, J.T.P., Deegan, T.D. (2021)
A conserved mechanism for regulating replisome disassembly in eukaryotes
Nature 600(7890): 743-747