Regulators of the cell cycle
Cells divide continuously throughout the life of an organism, allowing it to grow larger and to replace old tissue. Cell growth and division is governed by the cell cycle. This cycle consists of several stages which must be precisely co-ordinated. Errors in cell cycle can lead to parts of chromosomes being altered or lost, causing cancers.
Leland Hartwell discovered a specific class of genes that control the cell cycle. Using a yeast, Saccharomyces cerevisiae, as a model organism, he isolated cells whose cycles were controlled by mutant genes. He identified over 100 genes involved in control of cell cycling. One of these determined the first step in the cycle and was called ‘start’. He also introduced the concept of ‘checkpoint’, which stops the cell cycle when DNA is damaged, after studying the sensitivity of the cells to irradiation.
Paul Nurse worked with Saccharomyces pombe, a yeast only distantly related to S cerevisiae. He identified the gene cdc2, and showed that it carried out the same role as Hartwell’s ‘start’ gene. Studying this gene, he discovered CDK, a key regulator of cell cycle which drives the process through modification of other proteins. He showed that the fundamental role of CDK in cells is largely unchanged by evolution, and occurs in animals and humans, as well as yeast.
Timothy Hunt discovered that CDK function was regulated by a class of proteins called cyclins. Using the sea urchin Arbacia, he showed that these proteins are formed and degraded during each cell cycle. Cyclins were eventually discovered in other species, including humans.