Scientists' best view of the normal cycle of cell division has come from research on yeast. The most dramatic stage of the cycle is mitosis (M), during which a cell's chromosomes, which contain its genes, are duplicated and two identical cells take shape. Mitosis was the first stage of cell division ever examined by biologists, although it is actually one of the shortest. Three other stages, all of which occur before mitosis, were identified in the 1950s: S, during which DNA is synthesized; G1, which appears even earlier in the cycle; and G2, the short period after DNA synthesis.

As Leland Hartwell suggested in the 1970s, there is also a START point, where the cell "decides" whether to replicate its DNA. Beyond this point, the cell is committed to entering the S phase. (In mammalian cells, this point is now called R, for restriction point.)

Passing through the restriction point is "like Caesar crossing the Rubicon— it's the point of no return," says Steven Dowdy, an HHMI investigator at Washington University in St. Louis. "When regulation is lost at this critical checkpoint in the cell cycle, you get malignancy or progress toward malignancy."

The cell division cycle has been compared to a circular highway that has signposts, checkpoints, exits, rest stops, and even detours. Cells that pass the restriction point and duplicate their DNA must face yet another checkpoint at the end of the G2 stage, when the duplicated DNA is examined for accuracy before the cell is allowed to enter mitosis. Both checkpoints are regulated by cdc2, the protein encoded by one of the genes that Hartwell identified in yeast.

After all the genes in yeast were sequenced in 1996, scientists took a fresh look at the cell division cycle and the genes that play a role in it. One team of researchers, led by Raymond Cho and Ronald Davis of Stanford University and their colleagues at Affymetrix, used DNA chips to monitor the activity of all 6,000 genes in a yeast cell as it progressed through cell division. Another team, led by Paul Spellman, Patrick Brown, David Botstein, and Bruce Futcher, used Brown's microarrays. Both teams identified several clusters of genes that turn on or off together during specific stages of cell division. The scientists are now searching for the regulatory elements that direct and coordinate this activity—elements that probably exist in humans as well.

Meanwhile, both teams have placed their data on the Web, in the expectation that genomic data sets of this sort will become increasingly valuable as more data accumulate. In such data, perhaps, lies the key to stopping cell division when it runs amok—and thereby preventing cancer.

— Maya Pines

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The Cell Cycle

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