Cyclin and Genetics

All molecular and cellular functioning in the body can be traced in some way to genetics. The role of cyclin and cyclin dependent kinases in the cell cycle is no different. While many researchers, including those at the MBL, were working on the cellular functioning of cyclin and its related molecules, others were working on the genetics behind those functionings.

The first work with the genetics behind cell cycle control occurred in 1970, when geneticist Lee Hartwell identified cell division (cdc) genes in yeast. Hartwell identified cdc genes by studying mutant yeast cells which arrested at particular points in the cell cycle, indicating that the genes controlling their progression through the cell cycle were somehow different than normal (Patterson, 2002). By 1974, Hartwell and his colleagues had identified 19 separated cdc genes responsible for regulating the cell cycle in yeast (Hartwell, 1974).

In 1975, geneticist Paul Nurse identified yeast mutants with a different set of genes - wee genes - rather than cdc genes. The wee1-50 mutants divided into smaller cells than normal, indicating that the cells entered mitosis too early and that their normal cell cycle control was disrupted (Greenwood, 2002). It was unclear, however, whether the wee1-50 mutation caused the overactivation of a molecule which inhibited mitosis in some way until the cell was large enough, or the inhibition of a molecule which pushed forward mitosis in some way (Nurse, 1975). Five years later, Nurse and Pierre Thuriaux answered part of that question when they found that the wee1 protein (coded for by the wee1 gene) inhibits mitosis (Nurse, 1980). And in 1986, Nurse and another geneticist, Paul Russell, showed that the gene cdc25 - and it’s corresponding protein - activate mitosis. So in wee1-50 mutants, the cells did not produce enough of the wee1 protein (which inhibits mitosis), and thus were pushed into mitosis early by the cdc25 protein.

By 1989, that process was understood more clearly and wee1 was identified as a kinase, an enzyme that modifies proteins by adding a phosphate to them. Cdc25 on the other hand, is a phosphatase, an enzyme which modifies proteins by removing a phosphate. Both wee1 and cdc25 act on maturation promoting factor (MPF), which is a complex made up of cyclin B and a cyclin dependent kinase. Wee1 inhibits MPF and cdc25 activates MPF and thus they both play important roles in regulating the start of the cell cycle.

Suggested citation
Abboud, Alexis. 2015. "Cyclins at the MBL". MBL History Project digital exhibit. http://history.archives.mbl.edu/exploring/exhibits/cyclins-mbl
Bibliography

What are Cyclins?

Early Work with Cyclins

Tim Hunt and His Discovery of Cyclin

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Cyclins and Genetics

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