Academic journal article Genetics

Paul Nurse and Pierre Thuriaux on Wee Mutants and Cell Cycle Control

Academic journal article Genetics

Paul Nurse and Pierre Thuriaux on Wee Mutants and Cell Cycle Control

Article excerpt

In 1974, Paul Nurse was searching for fission yeast mutants that were larger than normal when he instead found one that was smaller. This unexpected wee mutant (named for its discovery in Scotland) led Nurse to identify a critical regulator of the cell cycle, and helped him win a Nobel prize.

Starting his postdoc with Murdoch Mitchison in Edinburgh, Nurse was inspired to investigate the cell division cycle by Lee Hartwell's work in isolating and analyzing budding yeast mutants arrested at specific points in the cycle (Hartwell et al. 1973). Nurse looked for similar mutants in fission yeast by isolating cells that continued to grow without dividing, which made them unusually large. Nurse unexpectedly discovered a clump of much smaller cells that did not arrest but instead divided early-before the cells had reached their wild-type size (Nurse 1975). Nurse realized that mutations of this sort, which accelerated the cell cycle, held the key to understanding how cells coordinated their growth and division to maintain a constant average size. And, having made this connection, the 1980 GENETICS paper set out to deliberately look for more wee mutants. Nurse and Thuriaux isolated 50 new mutants with this phenotype and found that all but one lay in the previously identified weel gene. But the exception was informative: it was a dominant mutation in the cdc2 gene. Previously identified, recessive, mutations in this gene kept cells from dividing. This meant different mutations in the same gene could either prevent or accelerate division, suggesting that Cdc2 was a critical regulator of cell division. Genetic analysis suggested a simple model: the activity of Cdc2 was required to enter mitosis, and Wee1 was a dosage-dependent inhibitor ofCdc2 activity. Many years of subsequent work showed that this model was correct, and that the presence and activity of Cdc2 and Wee1 were conserved throughout eukaryotes. For these important insights, Nurse shared the 2001 Nobel Prize in Medicine or Physiology with Lee Hartwell and Tim Hunt.

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Literature Cited

Hartwell, L. …

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