Chromosome tug-of-war
Scientists at the Research Institute of Molecular Pathology (IMP) unravel further details in the regulation of cell division.
The genetic information of higher organisms is packaged in the cell’s nuclei in the form of chromosomes. The number of chromosomes per nucleus is characteristic for every organism. Certain roundworms, for example, manage with just four chromosomes, while some plants have more than a hundred. Humans are somewhere between these extremes with 23 pairs of chromosomes. Despite countless divisions, the number of chromosomes must be kept meticulously constant by the cells. Before a division starts, the chromosomes must therefore double so that they can be passed on evenly to the two resulting daughter cells. If a mishap occurs, the newly formed cells have either surplus or missing chromosomes. In the best case, such deviations result in the death of the cell, but they can also lead to serious congenital diseases or cancer. It is therefore not surprising that the complicated processes of cell division are investigated intensely by scientists.
At the IMP, a team of yeast geneticists led by Kim Nasmyth is investigating the cell’s regulatory mechanisms that normally guarantee a flawless cell division. Among other things, the researchers are concentrating on the sensitive phase following the duplication of chromosomes. At this point, the sister chromatids, which are still connected in pairs, have to be checked for defects and repaired if necessary. The chromosomes are then pulled apart by filamentous molecules (microtubules). For a long time, it remained a mystery which mechanism would hold the sister pairs together and how they would finally be separated and drawn to opposite poles.
The researchers at the IMP succeeded in identifying a kind of molecular adhesive. This substance, which was dubbed cohesin, keeps the pairs connected. At the same time, the microtubules, which attach to the centromeres of the chromosomes, exert a pull to the outside. The two forces cancel each other out as long as cohesin is intact. There is a real tug-of-war around the chromosomes, which are stretched in pairs in the division plane.
In the latest issue of the journal "Cell" (17.9.99), the IMP scientists explain how their discoveries have gradually led to a clearer idea of what happens during cell division. Research on yeast cells has enabled them to locate the exact chromosome-sites where the cohesin adheres. Not surprisingly, the adhesive was mainly found on the centromeres. These findings fit well with those described in an earlier article in "Nature" (Vol. 400, p. 37). There, the authors had reported how an enzyme called separin cuts up the cohesin and abruptly terminates the cohesion.
For the geneticist Tomoyuki Tanaka, there is now finally an explanation of how cells ensure that sister chromatids are always pulled away from each other with high precision and do not migrate together in one direction. Further investigations will have to show whether the behaviour of yeast is transferable to the human organism. The researchers hope that knowledge about these complex cellular mechanisms will then provide important insights into the development of cancer.
Original Paper
Tanaka T, Cosma MP, Wirth K, Nasmyth K.: Identification of Cohesin Association Sites at Centromeres and along Chromosome Arms. Cell, 17 Sept 1999.