PhD Studentship Project: Repair of replication-associated DNA double strand breaks



A studentship is available to study the underlying mechanisms of repair of replication-associated DNA double strand breaks (DSBs).  

DSBs are dangerous forms of DNA damage. A single unrepaired DSB is can be lethal to a cell and inaccurate repair of a DSB can result in mutations or chromosome rearrangements. Cells are particularly vulnerable to DSBs that occur during replication. The break has to be repaired and replication restarted as it is vital that all of the genome is copied. Restart can be at the expense of an increased error rate leading to mutations and an increase in genome rearrangements. Since such changes can lead to cancer it is vital that replication is coordinated with repair and restarts correctly.

The Murray lab uses site-specific assays in fission yeast to study the consequences of problems during replication for genome stability (Mizuno et al, 2013). We have set up a system where we can induce a break during replication at a specific place in the genome, either in the absence of an incoming fork generating a one-ended break, or when a converging fork can rescue it to form a two-ended DSB. This enables us to study the events involved in repair and restart in a genetic system. Since these processes are conserved we can use this system to model how human cells repair replication-associated breaks. As cancer cells are actively growing and often defective in DNA damage responses a knowledge of the processes involved in the repair of DNA breaks in S phase will in the long term inform the rational design of therapeutic agents.

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The student will receive training in state-of-the-art molecular and cell biology techniques, and will also benefit from close interactions with other groups at the Genome Damage and Stability Centre.

Applications with a good honours degree (2-1 or above) and an interest in genetics and live cell imaging are encouraged to apply. The studentship is restricted to EEA candidates who meet the resident labour market test. Please contact Jo Murray ([email protected]) for more information. 

Start date: September 2013

Closing date for applications 31 August 2013

References: Mizuno K, Miyabe I, Schalbetter SA, Carr AM, Murray JM. Recombination-restarted replication makes inverted chromosome fusions at inverted repeats. Nature. 2013 Jan 10;493(7431):246-9.

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