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How does the RIF1 protein stabilize replication forks to ensure accurate genome replication?


   School of Medicine, Medical Sciences & Nutrition

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  Prof Anne Donaldson, Dr Shin-Ichiro Hiraga  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

A Cancer Research UK-funded PhD studentship is available to investigate mechanisms that ensure accurate and stable DNA replication, a process crucial for multiplication of both normal and cancer cells. Because of its fundamental importance for cell division, DNA replication inhibition is a common strategy for cancer treatment, making it critical to understand the replication process. This project will examine the role of the protein Rif1 in ensuring stable DNA replication despite the many obstacles to replication fork progression present within eukaryotic genomes—including highly transcribed genes, damaged DNA, DNA of unusual structure, and tightly bound proteins. This investigation will utilize the powerful approach of yeast molecular genetic analysis to obtain insights and understand principles that will then be extended to study the DNA replication process in human cells.

The successful candidate will join an active, well-funded research team using the latest advanced technologies, and operating within an extended group of labs sharing interests in chromosome biology and its relation to cell growth. The research will be carried out in the Institute of Medical Sciences located at the Foresterhill campus of the University of Aberdeen. The institute is well-supported by various facilities such as Microscopy, Flow cytometry, Genomics and Proteomics. This PhD position represents an outstanding opportunity to obtain training in both yeast and human cell systems, while contributing to cutting-edge research relevant to cancer and other genome instability disorders. 

Informal enquiries are welcome and should be addressed to Professor Anne Donaldson ([Email Address Removed]). Enquiries should include a CV and should briefly outline your interest in the research area.

Essential background of student:

Good candidates will have a strong interest in mechanisms of chromosome maintenance, and will either have or be about to obtain a Masters or Undergraduate degree at 2.1 level (or equivalent), with lab research project experience in a suitable area (such as biochemistry, genetics, or molecular biology).

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APPLICATION PROCEDURE:

International applicants are eligible to apply for this studentship but will have to find additional funding to cover the difference between overseas and home fees (approximately £17,000 per annum)

  • Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php
  • You should apply for the Degree of Doctor of Philosophy in Medical Sciences to ensure your application is passed to the correct team
  • Please clearly note the name of the supervisor and exact project title on the application form. If you do not mention the project title and the supervisor on your application it will not be considered for the studentship.
  • Candidates should have (or expect to achieve) a minimum of a 2.1 Honours degree in a relevant subject. Applicants with a minimum of a 2.2 Honours degree may be considered provided they have a Merit/Commendation/Distinction as Master's level.
  • General application enquiries can be made to [Email Address Removed]

Funding Notes

The position is funded by a Cancer Research UK studentship that covers student stipend at £19,000 per annum for four years and University fees at domestic level. International applicants are eligible to apply for this studentship but will have to find additional funding to cover the difference between overseas and home fees (approximately £17,000 per annum)
Expected start date October 2022.
Candidates should have (or expect to achieve) an Honours undergraduate degree at minimum 2.1 grade (or equivalent) in a relevant subject. A Masters qualification (at Commendation or Distinction level) would be an advantage but is not essential.

References


• C. Monerawela, S. Hiraga, and A.D. Donaldson, A.D. Checkpoint phosphorylation sites on budding yeast Rif1 protect nascent DNA from degradation by Sgs1-Dna2. biorxiv https://www.biorxiv.org/content/10.1101/2020.06.25.170571v1.
• L.P. Watts, T. Natsume, Y. Saito, J. Garzon, Q. Dong, L. Boteva, N. Gilbert, M.T. Kanemaki, S. Hiraga and A.D. Donaldson (2020). The RIF1-Long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress. ELife doi 10.7554/eLife.58020.
• J. Garzón, C. Monerawela, S. Ursich, M. Lopes, S. Hiraga and A.D. Donaldson (2019). RIF1-Protein Phosphatase 1 prevents degradation and breakage of nascent DNA on replication stalling. Cell Reports, 27: 2558-2566.e4
• S. Hiraga, C. Monerawela, Y. Katou, S. Shaw, K.R.M. Clark, K. Shirahige and A.D. Donaldson (2018). Budding yeast Rif1 binds to replication origins and protects DNA at blocked replication forks. EMBO Reports, doi: 10.15252/embr.201846222.
• S. Hiraga, G.M. Alvino, F. Chang, H. Lian, A. Sridhar, T. Kubota, B.J. Brewer, M. Weinreich, M.K. Raghuraman & A.D. Donaldson (2014). Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex. Genes & Development 28: 372
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