Working in the brewer's yeast Saccharomyces cerevisiae, Hunter and colleagues Valentin Boerner and Nancy Kleckner of Harvard University, writing in the April 1 issue of Cell, show instead that the decision on whether or not to crossover is made at a much earlier stage: after the DNA is broken but before the ends of the breaks become stably intertwined with their partner chromosome. Once the decision is made, chromosomes are shepherded along to form Holliday junctions and then crossovers by a group of six proteins called the ZMMs.
In the same issue of Cell, Olga Mazina, Alexander Mazin and Stephen Kowalczykowski from UC Davis with Takuro Nakagawa and Richard Kolodner from the Ludwig Institute of Cancer Research at UC San Diego studied one of the ZMM proteins, Mer3, known to be important for crossover recombination to occur. They found that Mer3 unwinds the DNA double helix but works only in one direction relative to the broken DNA end. It blocks extension of the DNA strand in the opposite direction. Mer3 therefore helps to stabilize the Holliday junction structure and promotes crossover recombination, Hunter said.
The findings mean that the pathways to crossover and non-crossover recombination are distinct, and distinct from an early stage, Hunter said. That turns the textbook account of meiosis on its head, he said.
While researchers now have a better understanding of the process, how the decision is made remains a mystery, Hunter said.
"We're getting insights, but we're left with big questions," he said.