November 25, 2024

Wayne State researchers discover an enzyme’s critical role in cell division

Members and former members of principal investigator Dr. Joshua Bembenek, pictured at left in the top row, gather in his lab last summer.

Researchers at the Wayne State University School of Medicine investigating connections between regulation of cell division and aspects of embryo development to better understand diseases like cancer and birth defects have published a study detailing how the enzyme known as separase cuts the glue holding chromosomes together.

The study comes from the laboratory of Joshua Bembenek, Ph.D., an associate professor of Obstetrics and Gynecology and member of the C.S. Mott Center for Human Growth and Development.

John Bembenek, Ph.D., is the principal investigator on the study.

Dr. Bembenek and his team research human diseases that arise from abnormalities in chromosome number, based on defective cell division. When cells divide, there is a critical checkpoint at the beginning of anaphase, when chromosomes move to daughter cells, he said.

“Our work shows that the enzyme works like a scalpel in a surgeon’s hand rather than a blender that just turns on to chop things up, and that the timing and placement of this knife inside the cell is critical for its proper function,” he said.

The study, “Securin regulates the spatiotemporal dynamics of separase,” published in the Journal of Cell Biology, shows how separase moves to sites of action only seconds before it acts, and that it has two different functions during anaphase: chromosome segregation and exocytosis, both of which rely on precise localization for proper execution.

The work is related to his lab’s longstanding interest in the role of separase during cell division and its novel function during vesicle exocytosis his team identified.

“The textbook function of separase is chromosome separation and we show that the novel function is regulated by the same cell cycle pathway,” Dr. Bembenek said. “Our primary interest is understanding how cells behave in real time, using live cell imaging. We use imaging to understand how multiple aspects of cell division are coordinated by cell cycle regulators.”

The proper regulation of cell division is critical for cells to avoid aneuploidy, which causes genetic diseases such as Down syndrome and infertility and is also correlated with aggressive cancers.

The research could generate important insights into human disease that may lead to the development of more effective therapies and cures.

To learn more about the research, visit  https://www.bembeneklab.org

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