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  Understanding the roles of PrimPol in DNA replication restart


   School of Life Sciences

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  Prof A J Doherty  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

Trans Lesion Synthesis (TLS) DNA polymerases allow efficient bypass of lesions and structures that block DNA replication, enabling cells to survive major genotoxic stress thus maintaining genomic integrity. Human TLS polymerase mutations are associated with ageing and major human diseases, including cancer. We propose to characterize a novel family of DNA lesion bypass polymerases called PrimPol in the context of genome replication. We have accumulated substantial data implicating PrimPol in restarting DNA replication in higher eukaryotes (see references below).

Aims: The PhD student will work on an exciting project to uncover the specific roles played by PrimPol in human DNA replication processes and determine how, in conjunction with polymerases and factors, it functions to maintain efficient genome replication in human cells. This exciting multi-disciplinary project will train the student in biochemical, cellular and molecular approaches to enable them to identify PrimPol-specific pathways required for efficient lesion bypass during chromosomal replication in human cells, define the overlap with other TLS polymerase pathways, study the cellular consequences of mutating/deleting PrimPol and relate these insights to the development of human diseases, e.g. cancer.

The successful applicant will join the Genome Damage and Stability Centre, an internationally renowned Institute carrying out research on the response of cells to DNA damage, genome instability and its relationship to human disease. We provide a stimulating and supportive research environment and our expertise covers a wide range of experimental systems. Further information about our research can be obtained from our website at http://www.sussex.ac.uk/gdsc/.


Funding Notes

Apply for PhD in Genome Stability (2017-18 entry) using http://www.sussex.ac.uk/study/phd/apply.
Mention name of supervisor in “suggested supervisor” section. In funding mention sponsored or seeking funding. In Award details mention School of Life Sciences funded studentship. Include brief statement of interest (up to 2 pages), CV, two academic references, UG/PG transcripts, IELTS/TOEFL results if residing in EU. The studentship is for 3.5 years (full fee waiver, stipend Research Council equivalent rate). Only full time students will be accepted.

Applicants must have or expect to obtain a BSc Hons degree (2.1 or higher) in biochemistry, cell biology or genetics. UK/EU students only.

References

Guilliam, T.A. & Doherty, A.J. (2017) PrimPol—Prime Time to Reprime. Genes, 8, 20.
Bianchi, J., et al. (2013) PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication. Mol Cell 52, 566-573.
Schiavone, D. et al. PrimPol Is Required for Replicative Tolerance of G Quadruplexes in Vertebrate Cells. (2016) Mol Cell. 61,161-9.
For further queries contact: Professor Aidan Doherty (ajd21@sussex.ac.uk)

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