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Meiosis: Step by Step. The resulting gametes have one copy of each chromosome and a unique mix of genetic material.
“It's like speed dating,” Roeder says. “If the partner doesn't work, you get up and try the next one.”
Zip1 and the rest of the SC can't be entirely responsible for the whole process of chromosomes finding each other though—Roeder and others have shown that in the absence of SC proteins, matches are still made. “The synaptonemal complex is not what brings things together, it's the glue that finally cements them together,” explains Kleckner.
The surprises as to what Zip1 does are likely to keep coming. The protein appears to play many different roles during meiosis. In recent experiments, Roeder identified two proteins that keep Zip1 from zipping up mismatched chromosomes. Her next goal is to figure out how those proteins work at the molecular level. Their mechanics may, in turn, reveal just how Zip1 acts as a chromosome zipper.
While the earliest meiosis researchers would surely be surprised by the intricate molecular interplay that controls meiosis, they might be just as astonished at the new techniques used to study it and how interdisciplinary the field has become.
“Different people in the modern era have brought to the table all different perspectives and points of view,” says Kleckner. Some scientists look at meiosis with an interest in regulatory molecules, she says, while others want to see the bigger picture of chromosomal movement.
HHMI investigator Abby Dernburg at the University of California, Berkeley, uses her microscopy background to study meiosis the old-fashioned way: through a lens. But where microscopes of the 19th century revealed only fuzzy movements of dark Xs and Ys within a cell, Dernburg can show a much clearer picture of meiosis with fluorescence, three-dimensional visualization, and higher-powered lenses.
Dernburg's study system of choice is the roundworm Caenorhabditis elegans, which boasts larger chromosomes than yeast cells—“so you can see clearly what's going on,” she says. Plus, it's easy to genetically manipulate worms and see the consequences for meiosis.
Dernburg's research focuses on “pairing centers” in C. elegans—regions on each chromosome that are essential for the zipping-up between chromosomes (the role Roeder thinks Zip1 plays at centromeres in yeast). In worms, the pairing center helps chromosomes find their matches (pairing) and then cement their connection (synapsis). The two processes are distinct from one another, says Dernburg. “You can get synapsis between improperly paired chromosomes and you can also have situations where the chromosomes pair but they don't synapse, because components are missing.”
The worm's pairing centers, she has found, seem to tether the chromosomes to the edge of the nucleus. She thinks they attach, through the nuclear membrane, to proteins outside the nucleus, and tug on chromosomes. Correctly matched pairs of chromosomes could resist this force, but others would be pulled apart until they found a stronger match. Through advanced microscopy techniques, Dernburg plans to investigate the strength of this tension.
Image: Adapted from http://publications.nigms.nih.gov/thenewgenetics