YEAST GENETICS

Yeast genetics provides an excellent model for the study of the genetics of growth in animal and plant cells. The yeast Saccharomyces cerevisiae is similar to animal cells (e.g., similar length to the phases of its cell cycle, similarity of the chromosomal structures called telomeres). Another yeast, Saccharomyces pombe is rather more similar to plant cells (e.g., similarities in their patterns of division, and in organization of their genome).

As well as being a good model system to study the mechanics of eukaryotic cells, yeast is well suited for genetic studies. Yeasts are easy to work with in the laboratory. They have a rapid growth cycle (1.5 to two hours), so that many cycles can be studied in a day. Yeasts that are not a health threat are available, so the researcher is usually not in danger when handling the organisms. Yeasts exist that can be maintained with two copies of their genetic material (diploid state) or one copy (haploid state). Haploid strains can be mated together to produce a diploid that has genetic traits of both "parents." Finally, it is easy to introduce new DNA sequences into the yeast.

Genetic studies of the yeast cell cycle, the cycle of growth and reproduction, are particularly valuable. For example, the origin of a variety of cancers is a malfunction in some aspect of the cell cycle. Various strains of Saccharomyces cerevisiae and Saccharomyces pombe provide useful models of study because they are also defective in some part of their cell division cycle. In particular, cell division cycle (cdc) mutants are detected when the point in the cell cycle is reached where the particular protein coded for by the defective gene is active. These points where the function of the protein is critical have been dubbed the "execution points." Mutations that affect the cell division cycle tend to be clustered at two points in the cycle. One point is at the end of a phase known as G1. At the end of G1 a yeast cell becomes committed to the manufacture of DNA in the next phase of the cell cycle (S phase). The second cluster of mutations occurs at the beginning of a phase called the M phase, where the yeast cell commits to the separation of the chromosomal material in the process of mitosis.

Lee Hartwell of the University of Washington at Seattle spearheaded the analysis of the various cdc mutants in the 1960s and 1970s. His detailed examination of the blockage of the cell cycle at certain points—and the consequences of the blocks on later events—demonstrated, for example, that the manufacture of DNA was an absolute prerequisite for division of the nuclear material. In contrast the formation of the bud structures by Saccharomyces pombe can occur even when DNA replication is blocked.

Hartwell also demonstrated that the cell cycle depends on the completion of a step that was termed "start." This step is now known to be a central control point, where the cell essentially senses materials available to determine whether the growth rate of the cell will be sufficient to accumulate enough material to permit cell division to occur. Depending on the information, a yeast cell either commits to another cycle of cell growth and division or does not. These events have been confirmed by the analysis of a yeast cell mutant called cdc28. The cdc28 mutant is blocked at start and so does not enter S phase where the synthesis of DNA occurs.

Analysis of this and other cdc mutations has found a myriad of functions associated with the genetic mutations. For example, in yeast cells defective in a gene dubbed cdc2, the protein coded for by the cdc2 gene does not modify various proteins. The absence of these modifications causes defects in the aggregation of the chromosomal material prior to mitosis, the change in the supporting structures of the cell that are necessary for cell division, and the ability of the cell to change shape.

Studies of such cdc mutants has shown that virtually all eukaryotic cells contain a similar control mechanism that governs the ability of a cell to initiate mitosis. This central control point is affected by the activities of other proteins in the cell. A great deal of research effort is devoted to understanding this master control, because scientists presume that knowledge of its operation could help thwart the development of cancers related to a defect in the master control.