Research Overview

Fig 1: Group photo

Fig 2: Colocalisation of Rad9 and Rad52 in S. cerevisiae

DNA damage results in mutations, which in turn can activate proto-oncogenes or inactivate tumour suppressors. The balance of activity of these genes determines the cancerous state. The DNA Damage Response (DDR) is a complex, interacting network of biochemical pathways that ultimately prevents the accumulation of cells with mutations. This response constantly surveys the genome for damage that threatens its stability.

Once structural alterations have been sensed there are five broad biological outcomes: 1) DNA repair; 2) transient delays to cell cycle progression (termed checkpoints); 3) a transcriptional programme; 4) programmed cell death (apoptosis) and 5) senescence. Failure to properly integrate these biological responses results in genome instability, the principal hallmark of cancer.

We investigate the mechanisms of sensing and responding to DNA damage Using yeast and, more recently, DT40 chicken cells as our principal model systems. Our research is a balance of hypothesis and discovery led research using both genetic and biochemical approaches to functionally and structurally analyse the role of checkpoint mediators, the central protein kinase regulators and the epigenetic regulation of the DDR.