Three scientists who provided fundamental insights into how and when cells divide have won this year's Nobel Prize in physiology or medicine. The Nobel Assembly at Stockholm's Karolinska Institute announced Monday that Leland Hartwell, director of the Fred Hutchinson Cancer Research Center in Seattle, Washington; Sir Paul Nurse, director-general of the Imperial Cancer Research Fund in London; and Timothy Hunt, also of the Imperial Cancer Research Fund, would share this year's prize "for their discoveries of key regulators of the cell cycle." The cell cycle is the process by which cells grow, replicate their DNA, and finally divide in two. Understanding this process is vital to figuring out why cell division sometimes runs amok, causing cancers.
In the late 1960s, Leland Hartwell was studying the genetics of baker's yeast, Saccharomyces cerevisiae, when he discovered mutations that appeared to stop the process of cell division at a certain point in the cell cycle. Those mutant yeast led him, with several colleagues, to discover dozens of so-called cell division cycle (CDC) genes.
In the mid-1970s, Paul Nurse discovered that many of the genes controlling cell division in fission yeast, Schizzosaccharomyces pombe, were nearly identical to those in S. cerevisiae, even though the two species last had a common ancestor more than 1 billion years ago. That implied that the genes are highly conserved throughout evolution and might also be similar in other organisms. In particular, a gene that Nurse called cdc2, which regulates several key phases of the cell cycle, turned out to be identical to one of Hartwell's discoveries, dubbed cdc28. In 1987, Nurse demonstrated the universality of this gene by isolating the corresponding human version and showing that if it is inserted into S. pombe, the yeast continues to function. Nurse also showed that the cdc2 gene codes for a so-called kinase protein, which works by adding or removing phosphate groups from other proteins.
Working with sea urchins, Tim Hunt in the early 1980s discovered cyclins, a group of proteins that help to regulate the kinases discovered by Hartwell and Nurse--now known as cyclin-dependent kinases (CDKs). "It is the cyclins that give instructions to the CDKs and tell them what to do," says Stephen Elledge of Baylor College of Medicine in Houston. Hunt discovered that the level of cyclin proteins in the cell periodically rises and falls, thanks to a system that breaks the proteins down--a process called proteolysis.
The announcement did not surprise colleagues. "It was obvious that these guys were going to get this prize," says Ted Weinert of the University of Arizona in Tucson. The work has provided scientists with vital clues about how and why the process of cell division goes awry in cancer, Weinert says. "Without these discoveries," he says, "cancer research would still be in the dark ages of watching cells and wondering."