The nature of conditionally lethal temperature-sensitive mutations in somatic cells

The usefulness of conditionally lethal mutations for the examination of structure-function relationships in biological materials was first recognized by Edgar and Lielausis ('64), who exploited such mutants extensively for studies in bacteriophage T4. The many advantages of this class of mutants have been previously described. The general value of this approach has been amply demonstrated by investigations with bacteriophages, bacteria, Drosophila, yeasts and, more recently, somatic cells. However, one important property of the conditionally lethal systems does require emphasis, and that is, that theoretically a large fraction of the genome should be susceptible to such lesions. In theory, therefore, a large number of functions involved in the cell cycle should be subject to analysis by isolation and study of conditional lethal mutants. In somatic cells, nearly all of the studies have involved mutants of the temperature-sensitive (ts) variety. We show the spectrum of ts cell-cycle mutants which have already been obtained, and emphasize two facets of these findings, namely, that the mutants involve a variety of steps in the cell cycle, and that several different cell lines can give rise to such mutants. In no instance, however, has the precise molecular defect been defined. Given these preliminary successes, it is appropriate to speculate as to the long-term perspective of this approach both in respect to the gamut of cell-cycle mutants which will be obtainable in this way, and the variety of cell lines which will prove useful in this regard.