When yeast are starved, they turn to sex to mix up their genes. But first they undergo meiosis to reduce their chromosome number in half before fusing with a mate. Just after the chromosomes are separated, a protein structure—the kinetochore—that is assembled on the chromosomes for microtubule attachment during cell division is shed. In Molecular Biology of the Cell online on July 8, ASCB member Dean Dawson and colleagues at the Oklahoma Medical Research Foundation found orchestrators of kinetochore shedding. Understanding meiosis in yeast could promote the understanding of birth defects resulting from chromosome segregation errors, Dawson believes.
When yeast cells enter meiosis the kinetochores release from the microtubule organizing center all at once. Previous studies had shown that a conserved kinase, Ipl1/Aurora-B, is involved in kinetochore release. The question, said Dawson, was, “Does Ipl1 control this release mechanism? Does it cause the proteins to fall off? We interrogated almost all the proteins in the kinetochore using quantitative mass spec, to pinpoint the interface of what’s lost and what is retained. We found that, indeed, Ipl1 is necessary for kinetochore release.”
Dawson continued, “In humans, most birth defects are the result of meiotic chromosome segregation errors. Many times this involves inappropriate separation of the sister chromatids. This [kinetochore release] is one mechanism that controls how the sisters separate; it’s conceivable that the molecular underpinnings of this process could shed light on how sister chromatids are separated in mammalian cells as well.”
For Dawson, this work is another important piece of the chromosome separation puzzle that he has been piecing together throughout his career. “I started working on meiosis 20 years ago when artificial chromosomes were discovered in yeast, and I could do experiments that no one had done before with these artificial chromosomes,” Dawson recalled. And there are still more experiments to be done to understand meiosis and mitosis in yeast. “One thing that is perplexing to us is that this kinase, Ipl1, that controls the regulated shedding of the outer kinetochore, is present in mitosis too, but the kinetochore is not shed in the same way. It remains a mystery how Ipl1 triggers this shedding meiosis but not mitosis,” Dawson said.
About the Author:
Christina Szalinski is a science writer with a PhD in Cell Biology from the University of Pittsburgh.