One for you, one for me

Each time a cell divides—and it takes millions of cell divisions to create a fully grown human body from a single fertilized cell—its chromosomes have to be accurately divided between both daughter cells. Assistant Investigator Sue Jaspersen, PhD, and her collaborators used, ironically enough, the single celled organism Saccharomyces cerevisiae—commonly known as baker’s yeast—to gain new insight into the process by which chromosomes are physically segregated during cell division.

The Stowers researchers found that a protein known as Mps3 not only ensures that cells have two functional spindle pole bodies, which generate the mitotic spindle apparatus that helps pull the chromosomes apart, but also that both spindle pole bodies are properly anchored in the nuclear membrane.

"When you enter mitosis, you need to have two spindle pole bodies on which you can pull the chromosomes. If you don’t, the probability of errors in chromosome segregation increases exponentially,” explains Jaspersen. “Even small mistakes can lead to birth defects, genetic instability and cancer.”

Unlike DNA molecules which serve as templates for the production of identical copies, the spindle pole body is a large protein structure composed of soluble proteins and so-called integral membrane proteins, which are anchored in the nuclear envelope. When the researchers introduced a specific Mps3 mutation into yeast cells, they found that, although their DNA had been duplicated, these cells had multiple duplication defects, including blocking insertion of the spindle pole body into the nuclear envelope.

What was most striking, however, was that nearly every cell examined had nuclear membranes that were, essentially, overgrown—with two to eight layers of nuclear envelope, and multiple lobes and extensions—instead of a simple spherical structure suggesting the Mps3 was remodeling the nuclear membrane to accommodate the spindle pole body.

The study was published in the Nov. 17, 2011 issue of PLoS Genetics.