airs entwined during meiosis. Green spots show the location of RNF212. (Neil Hunter/UC Davis)The latest paper from Hunter's lab, published Feb. 10 in Nature Genetics
, shows that Rnf212 is essential for crossing-over in mammalian cells. Crossovers form by a process called homologous recombination, in which chromosomes are first broken and then repaired by coupling with a matching template chromosome. Although hundreds of recombination events are started in each cell, only one or two crossovers will form between any given pair of chromosomes.
"There isn't a special, predetermined site for a crossover. It can occur just about anywhere along a chromosome. But there has to be at least one and there always is," Hunter said.
In a series of experiments in mouse cells, graduate student April Reynolds, Hunter and colleagues found that the RNF212 protein defines where crossovers will occur by binding to just one or two recombination sites per chromosome where it triggers the accumulation of the protein machinery that actually carries out the cutting and splicing of DNA.
Mice that lacked the gene for RNF212 were sterile. Mice that had one working copy of the gene were fertile, but on careful examination there were fewer crossovers formed while sperm and eggs were being made than in normal mice, potentially reducing fertility. It's possible that this might be tied to some causes of infertility in humans.
It remains unclear how each pair of chromosomes always manages to crossover at least once. But Hunter says he is, "convinced that RNF212 holds the key to understanding this unique problem in chromosome biology."
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