Nobel prize: Physiology or medicine

Since the 19th century, scientists have known that cells multiply by dividing. In recent decades, they’ve uncovered many of the proteins that initiate this replication process and ensure that one step follows another. Moreover, researchers have uncovered how problems such as cancer can crop up when cell division goes awry.

In cell division, a resting cell (top) begins to synthesize DNA (right). It duplicates the chromosomes (bottom) that segregate into two identical cells (left). Proteins called cyclins and cyclin dependent kinases (CDKs) direct the process. The Nobel Foundation

Three scientists who made advances in these areas will share the 2001 Nobel Prize in Physiology or Medicine. They are Leland H. Hartwell of the Fred Hutchinson Cancer Research Center in Seattle and Paul M. Nurse and R. Timothy Hunt, two researchers at the Imperial Cancer Research Fund in London.

In the early 1970s, Hartwell identified genetic mutations that disrupt cell division in yeast. That led other researchers, including Nurse and Hunt, to investigate these and other genes and the proteins they encode. In so doing, the three scientists discovered molecular machinery that orchestrates cell proliferation, says molecular biologist Stephen J. Elledge of the Howard Hughes Medical Institute and Baylor College of Medicine in Houston.

For a cell to replicate normally, it first copies its DNA to make duplicate chromosomes and segregates them. Implementing these or other steps of the so-called cell cycle out of order can result in aberrant chromosomes that may cause a range of maladies from birth defects to tumors. Indeed, the work of the three new winners has spawned several lines of research on cancer, which can arise when cell division remains unchecked.

After discovering that mutations could sabotage cell division, Hartwell went on to find more than 100 genes that encode proteins influencing the cell cycle. The primary value of this early work, Hartwell told Science News, was “to show that you could apply genetics to a very complicated problem,” such as cell division.

He and others also found some genes for so-called checkpoint proteins, which suspend the cell cycle to allow for DNA repair. A few years later, Nurse identified one of Hartwell’s cell cycle genes in another yeast, worked out its function, and eventually found its human version. This gene encodes a protein called cyclin dependent kinase 1, or CDK 1.

In the early 1980s, Hunt discovered cyclins, proteins that are produced and degraded cyclically. When cyclins bind to CDK molecules, “this complex activates a bunch of proteins,” Elledge says. “That starts the duplication of chromosomes, making two copies of everything.”

Since concentrations of CDKs remain steady in cells, it is the varying amount of cyclin that regulates how much cyclin-CDK binding occurs and thus determines whether the cell proceeds to divide. “That was a big breakthrough,” because it identified for scientists molecules governing cell division, says Bruce Stillman, director of Cold Spring Harbor Laboratory in Cold Spring Harbor, N.Y. Since then, researchers have found more CDKs, cyclins, and other proteins that affect the cell cycle. Therefore, he says, some of these proteins and their genes make inviting targets for drugs to thwart cancer.

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