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Paul Nurse and Pierre Thuriaux on wee Mutants and Control

Andrew Murray1 Molecular and Cellular and Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138

ORIGINAL CITATION Regulatory Genes Controlling in the Fission Yeast Schizosaccharomyces pombe and Pierre Thuriaux November 1, 1980 96: 627–637

n 1974, Paul Nurse was searching for fission yeast mutants vent or accelerate division, suggesting that Cdc2 was a critical Ithat were larger than normal when he instead found one regulator of cell division. Genetic analysis suggested a simple that was smaller. This unexpected wee mutant (named for its model: the activity of Cdc2 was required to enter mitosis, and discovery in Scotland) led Nurse to identify a critical regula- was a dosage-dependent inhibitor of Cdc2 activity.Many tor of the cell cycle, and helped him win a . years of subsequent work showed that this model was correct, Starting his postdoc with in , and that the presence and activity of Cdc2 and Wee1 were Nurse was inspired to investigate the cell division cycle by Lee conserved throughout eukaryotes. For these important in- Hartwell’s work in isolating and analyzing budding yeast mu- sights, Nurse shared the 2001 Nobel Prize in Medicine or Phys- tants arrested at specific points in the cycle (Hartwell et al. iology with Lee Hartwell and . 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 Literature Cited clump of much smaller cells that did not arrest but instead divided early—before the cells had reached their wild-type Hartwell, L. H., R. K. Mortimer, J. Culotti, and M. Culotti, size (Nurse 1975). Nurse realized that mutations of this sort, 1973 Genetic control of the cell division cycle in yeast: V. ge- netic analysis of cdc mutants. Genetics 74: 267–286. which accelerated the cell cycle, held the key to understanding Nurse, P., 1975 Genetic control of cell size at cell division in yeast. how cells coordinated their growth and division to maintain a 256: 547–551. 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 Further reading in GENETICS this phenotype and found that all but one lay in the previously identified wee1 gene. But the exception was informative: it was Fantes, P. A., and C. S. Hoffman, 2016 A brief history of Schizo- saccharomyces pombe research: a perspective over the past adominantmutationinthecdc2 gene. Previously identified, 70 years. Genetics 203: 621–629. recessive, mutations in this gene kept cells from dividing. This Hoffman, C. S., V. Wood, and P. A. Fantes, 2015 An ancient yeast meant different mutations in the same gene could either pre- for young geneticists: a primer on the Schizosaccharomyces pombe model system. Genetics 201: 403–423.

Copyright © 2016 by of America GENETICS doi: 10.1534/genetics.116.197186 Other articles by P. Nurse and P. Thuriaux Photo of Paul Nurse (left) and Pierre Thuriaux (right) courtesy of Paul Nurse. 1Address for correspondence: Molecular and Cellular Biology and Faculty of Arts and Feilotter, H., P. Nurse, and P. G. Young, 1991 Genetic and molec- Sciences Center for Systems Biology, Harvard University, Dr. 16 Divinity Ave., Room ular analysis of cdr1/nim1 in Schizosaccharomyces pombe. Ge- 3000, Cambridge, MA 02138. E-mail: [email protected] netics 127: 309–318.

Genetics, Vol. 204, 1325–1326 December 2016 1325 Gudenus, R., S. Mariotte, A. Moenne, A. Ruet, S. Memet et al., Kohli, J., H. Hottinger, P. Munz, A. Strauss, and P. Thuriaux, 1988 Conditional mutants of RPC160, the gene encoding the 1977 Genetic mapping in Schizosaccharomyces pombe by mi- largest subunit of RNA polymerase C in Saccharomyces cerevi- totic and meiotic analysis and induced haploidization. Genetics siae. Genetics 119: 517–526. 87: 471–489. Kalogeropoulos, A., and P. Thuriaux, 1985 Gene conversion at thegraylocusofSordaria fimicola: fit of the experimental data to a hybrid DNA model of recombination. Genetics 109: 599– 610. Communicating editor: C. Gelling

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