Eukaryotic cells make a single copy of their chromosomes in each cell cycle, using a large molecular machine known as the replisome. Unlike other cellular machines such as the ribosome or the proteasome, the replisome is assembled in situ on its substrate and then is disassembled once its job is complete, so that replication happens just once. In mammalian cells, replisome disassembly is controlled by two ubiquitin ligases, called CUL2-LRR1 and TRAIP, which are regulated in very different ways. CUL2-LRR1 drives replisome disassembly during DNA replication termination, whereas TRAIP activates a variety of important DNA repair pathways that are dependent upon replisome disassembly, both during S-phase and upon entry into mitosis. Building on our recent studies of replisome disassembly in budding yeast (Deegan et al, 2020) and in metazoa (Sonneville et al, 2019), this project aims to reconstitute the ubiquitylation and disassembly of the mammalian replisome with purified proteins, in order to dissect the underlying mechanisms and regulation.
At the MRC PPU, as well as the possibility of a PhD in one particular lab, we offer the possibility of two 4.5-month rotations in labs of their choice. A range of other projects from MRC PPU scientists are advertised on this website. Rotations provide valuable experience and help with deciding on the choice of PhD project and research group.
Please send a CV with contact details of three referees to and a cover letter explaining why you have chosen to apply to MRC PPU to firstname.lastname@example.org. The closing date for applications is 30th April 2021. Application from overseas students are welcome.