Biomedical Frontiers: Fall 1996, Vol.4, No.1
Checking the Cell Cycle

Research on a rare genetic disorder may help scientists better understand cell cycle checkpoints, which, in turn, may hold a key to understanding and preventing cancer. Dr. Jean Gautier, assistant professor of genetics and development (in dermatology), is studying the gene involved in Ataxia-telangiectasia (AT), an autosomal recessive disorder that affects children. AT causes many symptoms, including neurological abnormalities and deficiencies in the immune system, and is associated with a higher incidence of certain types of cancer

"There is a lot of evidence that the gene associated with AT is also important for DNA cell cycle checkpoints."

"There is a lot of evidence that the gene associated with AT is also important for DNA cell cycle checkpoints," says Dr. Gautier. For instance, mechanisms at the checkpoints ensure that every phase of the cell cycle is properly completed; if these mechanisms aren't working correctly, the cell will continue to divide despite the presence of errors that can creep into the DNA. Such an inability to stop cells from dividing could lead to cancer since cells can only repair these errors efficiently when they are not dividing. Half of all individuals with AT die of cancer in their 20s. Furthermore, epidemiological studies have found that people who have one mutated allele of the AT gene have a higher incidence of cancer, especially breast cancer among women.

To help unravel the checkpoint mechanisms, Dr. Gautier is studying how the AT gene functions using concentrated extracts from eggs of the frog Xenopus laevis. Because the eggs, when fertilized, divide quickly and synchronously, the extract oscillates between a mitotic state and a DNA synthesis state. "This allows us to look at signal transduction pathways in which AT is involved," says Dr. Gautier.

Another interesting aspect of the mutated gene responsible for AT is that it causes the degeneration of Purkinje cells--one of the most abundant cells in the cerebellum--which in turn results in ataxia. "It's puzzling as to why this gene is important to the function of Purkinje cells and to cell cycle checkpoints," says Dr. Gautier. Dr. Gautier is now beginning to clone a homolog of AT in Xenopus and hopes that this work in a very basic system far removed from humans could someday be applied to controlling cancer.