Calcium (pseudocolored from blue to orange) localizes to mitotic chromosome axes.

We know that cations associate with DNA and help to neutralize the negative charges of phosphate groups, but for the most part the analysis of cation effects has not gone any further. Now Strick et al. demonstrate that calcium is distributed on chromosomes in a particular pattern that may implicate it in regulating a chromosomal protein and thus chromosomal structure (page 899).

The author's method of choice is secondary ion mass spectrometry (SIMS). Unlike previous X-ray–based techniques, SIMS yields the depth and localization information characteristic of the results from a confocal microscope. It does so by first using a laser to displace a thin, localized layer of the material under study, and then using mass spectrometry to analyze the displaced material. Strick et al. refine this technique to measure isotopes of a number of cations, but the most interesting results come in the measurements of Mg2+ and Ca2+. Both are associated with mitotic chromatin, but Mg2+ is evenly distributed across the chromatin, whereas Ca2+ is concentrated at the AT-rich axis of each chromosome. This mimics the localization of certain chromosome scaffold proteins, including topoisomerase II (Topo II).

Leading up to mitosis, Topo II is needed to cleave and allow the untangling of DNA as it is condensed. But later in mitosis the activity of Topo II is turned off, perhaps changing the protein into a structural component that helps to keep the center of the condensed chromosome together.The basis of this inhibition was unknown. Now Strick et al. find that the altered ratio of Mg2+ and Ca2+ at the center of the chromosome is, at least in vitro, sufficient to shut off the cleavage activity of Topo II. Mitotic phosphorylation of Topo II may recruit Topo II to the chromosome but, when Ca2+ binds to the chromosomes during mitosis, this local increase in the concentration of Ca2+ may help to shut down Topo II activity. Although this model is appealing, it is yet to be proven, and there may be many other things that the concentrated calcium is doing at the central axis of the chromosome. ▪