Millions of cells in our body divide every day to replace cells that are injured, worn out, or dying. While cell division itself is a tightly regulated event that occurs as part of the cell cycle—the sequence of steps during which the cell duplicates its DNA and separates to form two new cells—serious errors occasionally occur.
Angelika Amon works to decipher the networks that regulate the accurate duplication of DNA and segregation of chromosomes during cell division. This information is crucial to understanding not only normal cell division, but also the uncontrollable cell division that leads to cancer. In particular, she is probing the way chromosomes are pulled apart as a cell divides to form two new "daughter" cells. "We want to determine how cells make sure their chromosomes separate in the right way," Amon said.
Cancer cells often acquire extra chromosomes, a form of genetic instability that drives cancer growth. The extra chromosomes are produced during cell division when the chromosomes don't separate correctly. While cells normally have an elaborate system of checks and balances to detect and fix such errors, many of these checkpoints are missing in cancer cells.
Amon's interest in chromosome segregation sprang from a high school biology class, where she watched an old movie of cells dividing. "I was fascinated by the movement of chromosomes and the apparent order and coordination involved in chromosomes joining and separating during cell division," Amon recalls.
Using the budding yeast Saccharomyces cerevisiae as a model, Amon combines genetic, cell biological, and biochemical techniques to determine the mechanisms that control the cell's progression from one stage of the cell cycle to the next. The yeast serves as an excellent model because the molecules involved in cell division are very similar to those involved in human cell division.
Her current focus is on chromosome segregation and the control of the final stage of cell division, called exit from mitosis, and the way the usual chromosome segregation process is modified to bring about the meiotic chromosome segregation program, a special form of cell division that yields an egg or sperm with only half the number of chromosomes that occur in the rest of the body's cells. When the egg and sperm unite, they bring together the full complement of an organism's chromosomes.
Amon and her colleagues have identified a protein known as Cdc14, which initiates the exit of cells from mitosis to the G1 phase. They have also identified two regulatory networks—FEAR and MEN—that promote the release of Cdc14. By studying this protein and its regulators, Amon hopes to unravel the mechanisms that control and coordinate the final stages of the mitotic cell cycle.
She also hopes to determine the mechanisms that ensure accurate chromosome segregation during meiosis. Missteps in the chromosome separation during this important cellular event are the leading cause of miscarriages and a major cause of birth defects, due to missing or extra chromosomes. Down syndrome, for example, occurs when an individual inherits three copies of chromosome 21, leading to mental and physical disabilities.
In addition, she wants to identify and characterize the genes that are required for the faithful execution of meiosis. "Understanding the molecular mechanisms that regulate chromosome segregation during meiosis may one day lead to ways to correct or modify their effects," she said. "The potential applications for dealing with genetic defects are very exciting."
