The use of conditional lethal cell cycle mutants of temporal and functional sequence mapping of cell cycle events

Conditional lethal mutants defective in particular steps of the cell division cycle have recently been isolated in several types of eukaryotic cells (Hartwell, '74; Nurse et al., '76; Frankel e t al., '76; Orr and Rosenberger, "76; Morris, '76; Sato, '76; Basilico, '77; Siminovitch and Thompson, '78). Among the several uses to which such mutants can be put is the derivation of temporal and functional sequence maps of cell cycle events. By a temporal map, I mean very simply a diagram summarizi. f: the temporal order of events during the cell cycle (fig. 11, such as could in principle be obtained by using a perfectly synchronous culture and methods for accurately and instantaneously monitoring each cell cycle event. Note that the temporal map per se provides no information on how the cell arranges for events to be carried out in an appropriate temporal order, or even on whether the temporal order indicated by the map is fixed or flexible. By a functional sequence map, I mean a diagram summarizing the functional interrelatedness of various cell cycle events. Figure 2 shows several possible examples. Note tha t a functional sequence map has implications for, bu t may not fully determine, the corresponding temporal map. For example, if three events occur in the dependent series A B: C,, then they must also occur in the fixed temporal order A then B then C. On the other hand, knowing that events A and B are in parallel pathways (fig. 2c) tells one nothing of their actual temporal order, and even suggests that the temporal order may be flexible. An unambiguous discussion of the use of conditional lethal cell cycle mutants for constructing temporal and functional sequence maps requires the recognition that there are several different times in the cell cycle that are relevant to consideration of any particular