For elements central to this control, homologs in other systems including humans are well-characterized and the fission yeast system has led in the initial identification of these elements. In a smaller way we are engaged in trying to isolate such homologs. The development of drug resistance is a major obstacle to the cure of many human cancers. Research in my laboratory is focussed on the investigation of mechanisms of resistance in human tumour cells, using a variety of molecular, biochemical, immunological and pharmacological approaches. A second form of resistance is mediated by alterations in the nuclear enzyme topoisomerase II, the subcellular target of many clinically important therapeutic agents.
Checkpoints are regulatory mechanisms that control transitions between cell cycle phases.
Each checkpoint is regulated by a signal transduction cascade which can trigger cell cycle arrest in the presence of cellular damage. The best characterized checkpoints detect incorrect DNA structures, including physically damaged DNA, incompletely replicated DNA, or improperly formed mitotic spindles. Many of the components of these signal transduction cascades have been conserved throughout eukaryotic evolution, as similar genes have been found to regulate these processes in yeast and man. The reason for the current intense interest in cell cycle checkpoint control is the association of defects in checkpoint control with human cancers. Genomic instability is a common feature accompanying checkpoint loss, regardless of which checkpoint is compromised, and whether or not the cell is subjected to exogenous stresses.