y attached to each other. One binds near the centromere and connects replicated chromosomes. The other binds to chromosome arms, where it coordinates recombination between maternal and paternal chromosomes.
Swi6 protects centromeres from recombination by letting the right proteins in to form the complex that attaches near the centromere while keeping the riffraff out. In this case, the riffraff is a specific protein that activates the complex responsible for recombination.
Swi6’s dual nature was difficult to clarify because of a completely counterintuitive observation: Removing Swi6 from the cell doesn’t result in more recombination near the centromere. This is because one of the proteins that Swi6 ushers in is found in both complexes and is required for recombination — but it relies on Swi6 to arrive at the centromere. Without Swi6, even if other proteins in the recombination complex get through, they lack this critical component and recombination still can’t go forward.
Photo courtesy of the Smith Lab
“Swi6 has both positive and negative roles,” said Smith. “Because of the strong negative role, you don’t get recombination. But if you take Swi6 away, you’ve lost the negative role but also the positive role, so you [still] don’t get recombination.”
A foundation for the future
The two-pronged strategy for preventing recombination near the middle of chromosomes “makes very good biological sense,” Smith said. “If you have something you really don’t want to do, you don’t put one lock on it, you put two.”
He expects that many other species besides yeast use a very similar strategy and even the same basic proteins. Mammals have versions of the same proteins that form those crucial molecular complexes, and what’s known about them so far syncs with what’s known about their fission yeast counterparts.
Smith doesn’t suggest that these similarities mean that his and Nambiar’s insights will quickly lead to new treatments for human patients, but he does point out that understanding how cells regulate the all-important process of sorting their chromosomes is the first step to understanding what goes wrong and what to do about it. Many advances in medicine, such as the recent progress in cancer immunotherapy, are built on foundations laid by basic scientists decades ago, he noted.
“Medicine in general is enabled by basic science,” Smith said.
This study was funded by the National Institutes of Health.
Sabrina Richards, a staff writer at Fred Hutchinson Cancer Research Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a Ph.D. in immunology from the University of Washington, an M.A. in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at email@example.com.
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