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  Determining the mechanisms that regulate DNA replication and minimise genome instability


   Sir William Dunn School of Pathology

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  Prof C Nieduszynski  No more applications being accepted

About the Project

A primary aim of our group is to understand how eukaryotic genomes are completely and accurately replicated, while ensuring coordination with transcription, epigenetic inheritance and repair of DNA damage. Errors during DNA replication give rise to mutations that cause genetic disease; failures directly underlie several human disorders; and DNA replication is the direct target of many chemotherapeutic agents. We use a combination of genetic, genomic, single-molecule, cell biology, bioinformatics and mathematical modelling approaches to elucidate mechanisms regulating genome replication – in both yeast and human cells. Current research within the group includes genetic screens to identify and then characterise novel regulators of DNA replication; the development of cutting-edge methods for the detection of DNA replication in single molecules; and the use of high-throughput sequencing and bioinformatics analysis to characterise regulators of genome replication and stability. A DPhil project would build upon our published discoveries and current research to determine the mechanisms that regulate DNA replication and minimise genome instability.

Funding Notes

4 Year DPhil Prize Studentships cover University and College fees, a stipend of ~£16,777 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See https://www.path.ox.ac.uk/content/prospective-graduate-students for full details and to apply.

References

Müller, CA, & Nieduszynski, CA (2017). DNA replication timing influences gene expression level. J Cell Biol, jcb-201701061.
Daigaku Y, Keszthelyi A, Müller CA, Miyabe I, Brooks T, Retkute R, Hubank M, Nieduszynski CA, Carr AM (2015). A global profile of replicative polymerase usage. Nature Structural & Molecular Biology, 22:192-8
Hawkins M, Malla S, Blythe M, Nieduszynski CA, Allers T (2013). Accelerated growth in the absence of DNA replication origins. Nature, 503:544-7.
Natsume T, Müller CA, Katou Y, Retkute R, Gierliński M, Araki H, Blow JJ, Shirahige K, Nieduszynski CA, Tanaka TU (2013). Kinetochores coordinate pericentromeric cohesion and early DNA replication by cdc7-dbf4 kinase recruitment. Molecular Cell, 50:661-74.

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