Stephen Taylor - Overview

The differences between cancer cells and normal cells do not merely arise due to an increase in cellular proliferation, but rather due to an accumulation of a large number of genetic alterations. Indeed, cancer cells have highly abnormal genomes, displaying aneuploidies, chromosome rearrangements and gene amplifications. These alterations accumulate because, at an early stage in the evolution of a cancer, a cell becomes genetically unstable. Indeed, it is now becoming increasingly clear that mutations in genes that monitor and maintain genome integrity underlies tumourigenesis. To maintain genome integrity, eukaryotes have evolved a series of surveillance mechanisms, called cell cycle checkpoints, which delay cell cycle progression in response to errors that may result in genetic damage. These delays then allow time for the errors to be corrected or, if the damage is irreparable, induce apoptosis, thus removing the damaged cell from the population. One of these checkpoints operates during mitotsis to ensure accurate chromosome segregation, thereby preventing the generation of aneuploid daughter cells. We have identified several human proteins involved in this checkpoint pathway, namely Bub1, Bub3 and BubR1. To determine how these molecules ensure accurate chromosome segregation we are employing a range of biochemical, cell biological and genetic approaches.