Recorded: 20 May 2004
Yes, initially [I worked with Paul Nurse.] He was isolating cell cycle mutants and I talked to Murdock [Mitchison] about his—Murdock wanted to, and I think he would have liked if I had studied growth which was his interest. And I opted to work with Paul and study cell cycle mutants. And at the time there was a visitor, a friend of Paul’s from Bern—see fission yeast genetics had been pioneered by Urs Leupold in Bern— and Paul had actually gone over to Bern to learn genetics. And the person in Leupold’s Lab who taught Paul fission yeast genetics was a man called Pierre Thuriaux. And Pierre at a later stage came over and spent a year or so in Edinburgh it may have been six months I can’t remember. He came over with his wife to Edinburgh. And what had happened is Paul had isolated some cell cycle mutants and I started analyzing a lot of them. And he and I found mutants that were defective in mitosis and mutants that were defective in DNA replication. And then Paul had isolated these mutants which could still divide but divided at a smaller size than normal and he very quickly worked out that these were very interesting mutants that they weren’t just cell shaped mutants. He quickly worked out that what normally happened during the cell cycle and fission yeast was that a cell would replicate its few chromosomes at the beginning of the cycle and then the cells would wait a very long period of time with replicated chromosomes before they would enter mitosis. And what he realized was that when he identified this gene which we now know as we1— which we now know to be a kinase that inhibits Cdk1. That when you didn’t have we1, the cell would replicate its chromosomes and then instead of waiting around it would go into mitosis very soon there after. And it was a beautiful experiment because he had temperature sensitive mutants in we1 and he could just raise the temperature and inactivate the protein and suddenly a whole series of cells that were sitting around in G2 would suddenly charge into mitosis. And so he realized, you know, it was just beautiful experiments. It told you immediately that we1 was inhibiting entry into mitosis and this was something completely new. Something that half or hadn’t been done. So he’d set out to just sort of copy Hartwell, and sort of through a complete accident he bumped into this different class of mutant. And what he bumped into was a way of getting at regulators of the cell cycle. And so then he isolated lots of mutants in we1, isolated lots of mutants that had the small cell phenotype and he realized there were two genes. There was, most of them the loss of functions in mutations of we1, and then there was one or two mutants that were gain a function mutations. That is they were dominant in a second gene which he called we2. And around this time Pierre had arrived in the lab. And Pierre was a geneticist and he realized well, we2 because they were dominant alleles, they must be alleles of a gene which might be involved in….in…that might be normally required to get a cell into mitosis. But these alleles were hyperactive so the cell would go into mitosis more rapidly and have the same effect as removing we1. And so what he did was he took the we2 mutants and crossed them to all the different cell cycle mutants that Paul and I had characterized to ask was it an allele of one of the various cdc genes so there was cdc 1 through 25 or whatever it was. And at the time cdc2 was just you know a cdc gene that was required for mitosis. And it was actually, Pierre— who I remember being in the lab that morning—he came in with a sort of grin as wide as a Cheshire cat and he said “Guess which gene we2 is allelic with?” This, Paul didn’t know this. I mean he knew Paul was doing these things, but Paul was off somewhere anyway and, you know, how could I guess? But anyway you know he said “Its cdc2!” And that was the point when suddenly the genetics that Paul had started and suddenly that’s when cdc2 became a very special gene. It became clear that if you didn’t have it you did not get into mitosis and you could mutate it in ways in which you would go into mitosis much more rapidly. And from that point on it was clear that we1 was regulating cdc2 and that cdc2 was a terribly important regulator of mitosis. And this wasn’t really anything to do with my work but this was the sort of ambience in which one was working.
Kim Nasmyth is the Head of the Biochemistry Department of the University of Oxford and the Whitley Professor of Biochemistry. He was educated in Great Britain and earned his Ph.D in Zoology from the University of Edinburgh. He did his postdoctoral studies in Ben Hall's labolatory in Seattle Washington. He spent one year at Cold spring Harbor Laboratories as a Robertson Fellow. He was the Director of the Research Institute of Molecular Pathology (IMP) in Vienna (Austria). He is one of the discoverer of cohesin, protein complex which during cell division is crucial for faithful chromosome segregation.
Professor Nasmyth is a fellow of the Royal Society and Foreign Honorary Member of the American Academy of Arts and Sciences. He has received many scientific honours, including the Max Perutz Prize, the Louis Jeantet Prize for Medicine and the Wittgenstein Prize and the Unilever Science Prize.
More information: Wikipedia