Cell Division Checkpoint Genes Regulate Chromosome Dispersal

Observation of cell division in yeast has revealed how a pair of genes works in tandem to ensure that the correct number of chromosomes is transferred to each daughter cell.

The spindle checkpoint ensures accurate chromosome segregation by delaying cell-cycle progression until all sister kinetochores capture microtubules from opposite poles and come under tension. Kinetochores are assemblies of at least 19 proteins on chromatids where the spindle fibers attach during cell division to pull sister chromatids apart.

Although the checkpoint is activated by either the lack of kinetochore-microtubule attachments or defects in the tension exerted by microtubule-generated forces, it has not been clear whether these signals were linked.

Investigators at the Oklahoma Medical Research Foundation (Oklahoma City, USA) used high-powered microscopy to elucidate the stages of chromosome-microtubule interactions and their regulation by the genes Ipl1/Aurora B and Mps1 through meiosis.

They reported in the January 31, 2013, online edition of the journal Science that Ipl1/Aurora B released kinetochore-microtubule (kMT) associations following meiotic entry, liberating chromosomes to begin homologous pairing. Surprisingly, most chromosome pairs began their spindle interactions with incorrect kMT attachments. Ipl1/Aurora B released these improper connections while Mps1 triggered the formation of new force-generating microtubule attachments.

"Ipl1/Aurora B and Mps1 genes act as quality controllers and master regulators. If they are removed, the entire process goes haywire," said senior author Dr. Dean Dawson, a member of the cell cycle and cancer biology research program at the Oklahoma Medical Research Foundation.

"When cells divide, they first duplicate the DNA, which is carried on the chromosomes. Think of the cell kind of like a factory. First it duplicates the chromosomes—so that each one becomes a pair, then it lines them up so the pairs can be pulled apart—with one copy going to each daughter cell. This way, one perfect set goes to each new daughter cell, ensuring that the two new cells that come from the division have full sets of the DNA," said Dr. Dawson. "The human body begins as a single cell. Through the process of cell division, we come to be composed of trillions of cells. And every one of those divisions must be perfect so that each new cell inherits a correct set of chromosomes. Given the sheer number of cell divisions involved, it is amazing there are not more mistakes. My laboratory is interested in dissecting the machine that does this so well and understanding why it fails in some rare cases."

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Oklahoma Medical Research Foundation