Establishment of Sister Chromatid Cohesion during DNA Replication
Dr F Uhlmann
Dr J Diffley
Tuesday, November 12, 2019
Funded PhD Project (Students Worldwide)
A joint Cric funded PhD position for the 2020 programme between the labs of Dr Frank Uhlmann & John Diffley.
Following DNA replication in S phase, the two replication products are held together by the chromosomal cohesin complex. This sister chromatid cohesion is essential for accurate chromosome segregation during cell division. In this project, we will use a biochemical approach to study molecular mechanisms of how sister chromatid cohesion is established during DNA replication.
Cohesin is a ring-shaped multisubunit ATPase complex that is thought to function by topologically entrapping the two sister chromatids. In budding yeast, cohesin is loaded onto chromatin in G1 phase by the Scc2-Scc4 cohesin loader complex. During DNA replication, an active process termed cohesion establishment turns cohesin into physical linkages between sister chromatids. In addition to the cohesin loader, cohesion establishment requires several DNA replication factors, including Ctf18-RFC, Tof1, Csm3, Mrc1, Ctf4, and Chl1.
Our laboratories have biochemically reconstituted the multi-stage process of chromosomal DNA replication, as well as the topological loading of cohesin rings onto DNA. Here, we propose a collaborative project between the two laboratories that investigates the molecular events that take place when the replication fork meets cohesin during DNA replication.
This project requires a strong interest in molecular mechanisms that underlie a fundamental cellular process. Experience with protein biochemistry will be an advantage
Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2020 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).
Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘APPLY NOW’ LINK ABOVE) BY 12:00 (NOON) 13 NOVEMBER 2019. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
Successful applicants will be awarded a non-taxable annual stipend of £22,000 plus payment of university tuition fees. Students of all nationalities are eligible to apply.
1. Uhlmann, F. (2016)
SMC complexes: from DNA to chromosomes.
Nature Reviews Molecular Cell Biology 17: 399-412. PubMed abstract
2. Yeeles, J. T. P., Janska, A., Early, A. and Diffley, J. F. X. (2017)
How the eukaryotic replisome achieves rapid and efficient DNA replication.
Molecular Cell 65: 105-116. PubMed abstract
3. Murayama, Y., Samora, C. P., Kurokawa, Y., Iwasaki, H. and Uhlmann, F. (2018)
Establishment of DNA-DNA interactions by the cohesin ring.
Cell 172: 465-477 e415. PubMed abstract