WHI3 Regulation of CDK in S. cerevisiae.

Abstract

There are many diseases associated with malfunc4ons in the cell cycle. For instance, aneuploidy—when daughter cells have the abnormal number of chromosomes—results from improper cell division. Diseases that arise from chromosomal abnormali4es range from Down Syndrome to Turner Syndrome to Patau Syndrome, all extremely debilita4ng afflic4ons. Another serious consequence of unregulated cell division is the development of cancers. One of the hallmarks of cancer cells is cell prolifera4on, which is a result of unregulated cell division. Studying cell cycle regula4on in yeast, par4cularly budding yeast, Saccharomyces cerevisiae, allows for a beFer understanding of the human cell cycle. Many of the genes studied in my lab are conserved in humans, meaning that those yeast cell proteins also func4on in human cells. Mito4c cell division—the type of division in which a mother cell produces two iden4cal daughter cells—is regulated by a protein complex called cyclin-dependent kinase (CDK). This protein complex has been intensely studied by cell biologists, yet there is s4ll much that is unknown about how it is controlled. CDK—which must be ac4ve in order for cell division to occur—is regulated by a protein in yeast called Swe1. Swe1 inhibits CDK when the cell is perturbed, thereby hal4ng cell division. One way that the cell can be perturbed is by the dele4on of the protein ELM1. When present, ELM1 regulates the cytoskeleton of the cell. However, when ELM1 is deleted, Swe1 is ac4vated, which results in a delayed cell division and irregularly long buds. These long buds are also the result of sep4n perturba4on. When func4oning properly, sep4n proteins form a ring around the bud neck. We recently found that the dele4on of another protein called WHI3 rescues the ELM1 dele4on-induced cell division delay and long buds. By u4lizing fluorescent microscopy, we have been able to visualize cells lacking both WHI3 and ELM1. Our hypothesis is that WHI3 is somehow involved in regula4on of CDK. In order to test this hypothesis, we are working on experiments to see what happens to CDK and other regulators of cell division when ELM1 is deleted, WHI3 is deleted, and when both WHI3 and ELM1 are deleted. I will be conduc4ng other molecular biology experiments to measure the level of CDK ac4vity in both the cytoplasm and the nucleus. My work will help to elucidate another mechanism by which CDK is regulated, which will contribute to our overall understanding of proper progression through the cell cycle.