Cell biologists show molecular forces are key to proper cell division

Studies led by assistant professor of Biology Thomas Maresca are revealing new details about a molecular surveillance system that helps detect and correct errors in cell division that can lead to cell death or human diseases. Findings are reported in the current issue of the Journal of Cell Biology.

The purpose of cell division is to evenly distribute the genome between two daughter cells. To achieve this, every chromosome must properly interact with a football-shaped structure called the spindle. However, interaction errors between the chromosomes and spindle during division are amazingly common, occurring in 86 to 90 percent of chromosomes, says Maresca, an expert in mitosis.

“This is not quite so surprising when you realize that every single one of the 46 chromosomes has to get into perfect position every time a cell divides,” he notes. The key to flawless cell division is to correct dangerous interactions before the cell splits in two.

Working with fruit fly tissue culture cells, Maresca and graduate students Stuart Cane and Anna Ye have developed a way to watch and record images of the key players in cell division including microtubule filaments that form the mitotic spindle and sites called kinetochores that mediate chromosome-microtubule interactions. They also examined the contribution of a force generated by molecular engines called the polar ejection force (PEF), which is thought to help line up the chromosomes in the middle of the spindle for division. For the first time, they directly tested and quantified how PEF, in particular, influences tension at kinetochores and affects error correction in mitosis.

“We also now have a powerful new assay to get at how this tension regulates kinetochore-microtubule interactions,” Maresca adds. “We knew forces and tension regulated this process, but we didn’t understand exactly how. With the new technique, we can start to dissect out how tension modulates error correction to repair the many erroneous attachment intermediates that form during division.”

Separation of a cell

This illustration shows a cell undergoing mitosis or “cell division.” The cell membrane is shown in blue, and the cell’s chromosomes are shown in yellow. Mitosis is a well-studied and well-imaged phenomenon in two-dimensional images, but it’s never before been seen quite like this. What makes this image special is the use of a new fluorescent protein called MiniSOG, shown flying out of the cell.

Image courtesy of Andrew Noske and Thomas Deerinck (National Center for Microscopy and Imaging Research, University of California, San Diego); Horng Ou and Clodagh O’Shea (Salk Institute).

(Source: MSNBC)