The Doherty Group

Molecular and cellular mechanisms of DNA double-strand break repair

DNA double-strand breaks (DSB) are a significant form of DNA damage. A single DSB has the potential to activate cell cycle checkpoint arrest and/or apoptosis and a single unrepaired DSB is potentially lethal to a cell. Inaccurate repair of a DSB has the potential to contribute to oncogenesis due to the loss or amplification of chromosome segments or by exchange of parts of chromosomal arms leading to translocations. DSB can arise either from exogenous DNA damaging agents, from by-products generated during general cellular metabolism, or during specific cellular processes, such as V(D)J recombination, replication or meiosis.

Our research programme is directed primarily at biochemical, cellular and structural studies of the non homologous end-joining (NHEJ) DNA repair pathways in both eukaryotic and prokaryotic organisms, which mediate the recognition and cellular response to DSB damage. We are working towards a better understanding of (i) the specific protein-DNA and protein-protein interactions involved in recognising the presence of DNA breaks, (ii) the  molecular choreography  of break processing and (iii) how the NHEJ repair pathway is  reciprocally regulated, with homologous recombination, through out the cell cycle.

Our research work is funded by: