Key to Proper Cell Division

Photo: Chromokinesin

This shows the expression of the chromokinesin
NOD (red) stabilizes aberrant interactions
between kinetochores and spindle microtubules
(green); © University of Massachusetts

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 said. 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 did not 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."

The cell biologists conduct their experiments inside living cells. In normal cell division, chromosomes line up in the center, where two copies of each chromosome are held together with "molecular glue" until signaled to dissolve the glue and divide. To oversimplify, each chromosome copy is then pulled to opposite poles of the cell, escorted in what looks like a taffy pull away from the center as two new daughter cells are formed.

During the split, molecular engines pull the copies apart along microtubule tracks that take an active role in the process that includes shortening microtubules by large, flexible scaffold-like protein structures called kinetochores that assemble on every chromosome during division. Maresca and colleagues say until this study revealed details, PEF's function as a kinetochore regulator has been underappreciated.; Source: University of Massachusetts at Amherst