Cramming your vacation wardrobe into your luggage is a breeze compared with the packing job cells perform. Before they can divide, they have to scrunch long DNA molecules into tiny chromosomes. The tangles that form in DNA molecules help this chromosome compression, Kawamura et al. report.
The team studies newt chromosomes—they are large and convenient to observe—that are packing masters. Jammed into a 10-micron–long chromosome is a meter-long DNA molecule. Proteins such as condensins bunch up the DNA. They aren't the whole story, however, since protein-degrading enzymes don't spur chromosomes to completely unravel. The DNA itself is tangled, and these knots might also help the chromosome stay taut, Kawamura et al. hypothesized.
To test the idea, the researchers sprayed isolated newt chromosomes with topoisomerase (topo) II. This enzyme untangles DNA knots by severing the double helix, slipping the uncut strand through the opening, and then sealing the break.
By pinning down one end of the chromosome and pulling on the other end, the team gauged topo II's effect on chromosome stretchiness. Topo II relaxed the chromosome by about 35%, as measured by the amount of force required to lengthen it a certain amount. However, topo II's cousins topo I and topo III, which can also loosen DNA, had little effect.
The results suggest that DNA knots collaborate with proteins to compact chromosomes. Topo II, which can tighten chromosomes in certain situations, might have a dual role in cells, compressing DNA early in mitosis and loosening it after the chromosomes have separated.