Studying a novel interaction between mediator of DNA damage checkpoint (MDC1) and the SAC effector BubR1 in cancer cells

Effective DNA damage sensing and repair is vital to the survival of our cells but can also lead to resistance to anti-cancer agents. DNA repair takes place in interphase and is thought to be largely repressed in mitosis due to the risk of telomere fusion. Preliminary data demonstrates that cancer cells exhibit a BubR1-dependent mitotic arrest following treatment with irradiation (IR) plus a Chk1 inhibitor. This demonstrates the existence of a novel DNA damage response in mitosis which could act as a final genomic fidelity check prior to cell division and lead to resistance to anticancer therapies such as radiotherapy by providing a means for the cancer cell to repair damage induced by the treatment.

Previously, there have been few links found between the DNA damage response and mitosis. The DNA damage checkpoint mediator MDC1 has been implicated in mitotic progression and shown to interact with BubR1 in a normal, unperturbed mitosis. I have demonstrated that MDC1 and BubR1 also interact following treatment with IR in mitotic cells. This project will further characterise the interaction and uncover the phenotypic consequences. The project will be based in the medical school but will involve working between the medical school and chemical and biological engineering, learning a range of cell biology and mass spectrometry techniques thus providing a broad training in translational oncology research

How to apply

Please complete a University Postgraduate Research Application form and attach at least two references to your application.

Please clearly state the prospective main supervisor in the respective box and select ‘Oncology & Metabolism’’ as the department.