Mitotic mischief: can cells divide without chromosomes?

Science News, August 31, 1996 by John Travis

Consider the role of the corpse at a funeral. Though the reason for the often elaborate proceedings, the corpse can do nothing to control the events taking place around it. In the end, its fate rests in the hands of the pallbearers.

In 1961, when discussing the role that chromosomes play in the splitting of a single cell into two, the late Daniel Mazia drew an analogy with corpses at funerals. At first blush, the idea of these threads of DNA as inactive participants in cell division seems improbable. After all, before a cell divides, its chromosomes must duplicate, separate into two sets, and move to opposite sides of the cell.

Do chromosomes, however, actually direct the drama of the dividing cell? Or are they, like the corpse, central but ultimately passive characters? Two research groups, both of which describe their work in the Aug. 1 Nature, have now made dramatic attempts to resolve this issue. One team observed what happens to the assembly of the spindle, an intricate structure needed for cell division, when plastic beads covered with DNA stand in for chromosomes. The second group performed the even more daring feat of asking cells to perform the final acts of cell division without chromosomes or even any substitutes.

The ability to divide properly may be the most important skill that cells possess. Without thousands upon thousands of perfect cell divisions, for example, the fertilized egg could not transform itself into a healthy baby.

While some cells, such as the brain's neurons, rarely divide in adults, biologists believe that every cell can double its contents and split in two if given the proper signals. Indeed, many cells spend the majority of their lives preparing for cell division. During interphase, the longest stage of the cell's life cycle, the cell stockpiles proteins and other crucial molecules.

It also copies its DNA. With that groundwork laid, the cell awaits the main act in the division process: mitosis.

Mitosis creates two nuclei from the cell's single nucleus. Its name derives from the Greek word for thread, because the first visible signs of mitosis under most microscopes are the disappearance of the boundary around the nucleus and the concentration of the nucleus' normally diffuse DNA, along with some proteins, into threadlike chromosomes.

"Cell division is a very dramatic phase in the life of the cell. When you get into mitosis, everything changes-the nuclear envelope breaks down, the chromosomes condense, the spindle forms," says Jeremy Hyams of University College London.

The spindle, one of the most photogenic, though temporary, cellular structures, is a football-shaped scaffold of long hollow rods. Called microtubules, the rods form from the protein tubulin. The spindle's microtubules line up the duplicated chromosomes in a plane across the center of the cell. This arrangement ensures that when they later disjoin and move apart, each half of the cell receives an identical set of chromosomes. The spindle is also necessary for this separation to occur, though its exact role is still hotly debated.

How does the elaborate spindle form? Biologists have long held that chromosomes were vital to this essential component of the cell division process. Most current theories of spindle assembly focus on the interplay between the centromeres, which are specific DNA sequences on chromosomes, and the centrosomes, sites of microtubule construction outside the nucleus.

In one explanation, known as the search-and-capture model, growing microtubules radiate out from two centrosomes at opposite ends of a cell.

Complexes of proteins at the centromeres then capture and stabilize the microtubules to create the spindle.

This model has derived support from many studies over the years, including ones in which chromosomes are removed from living cells. As the number of chromosomes decreases, so does the number of microtubules in the spindle, explains R. Bruce Nicklas of Duke University in Durham, N.C. This particular finding, however, doesn't distinguish what parts of the chromosomes are used to assemble the spindle.

Investigators from the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have crushed dozens of eggs in an attempt to resolve that issue. Specifically, they are working with the extracts of eggs from the African frog, Xenopus laevis. With such extracts, the scientists can monitor in a test tube the same cell cycle stages, including spindle assembly, that occur in frog cells.

Recently, Rebecca Heald and her colleagues at EMBL, including Anthony Hyman and Eric Karsenti, came up with the idea of removing the centrosomes and the chromosomes from the frog egg extracts. They replaced the chromosomes with beads coated with random sequences of DNA. Though the beads served as substitute chromosomes, the test-tube system lacked several of the elements that the proponents of the search-and-capture model thought necessary for spindle assembly. Among the missing elements were kinetochores, the complexes of protein at the chromosomes' centromeres.