Start point (yeast)

The Start checkpoint is a major cell cycle checkpoint in yeast. The Start checkpoint ensures irreversible cell-cycle entry even if conditions later become unfavorable. The physiological factors that control passage through the Start checkpoint include external nutrient concentrations, presence of mating factor/ pheromone, forms of stress, and size control.

In an effort to study the ordered events of the cell cycle, Leland Hartwell et al. screened for and characterized temperature sensitive mutants, also known as cell division cycle mutants (cdc mutants), that display arrested cellular development at various stages of the cycle. Hartwell not only identified the mutant, cdc28, which arrests in very early stages of the cell cycle, but he also recognised that the presence of mating factors could result in similar phenotypes of inhibited bud formation and lack of DNA synthesis. Notably, cells that were exposed to mating factors at later stages of the cycle continued division, and only arrested when the resulting daughter cells reached the “early stages” (or more technically, the G1 phase) of the cell cycle. These results suggest that both cdc28 and mating pheromones mediate such early events, and further suggest that there exists a point in the cell cycle where the cell commits to division rather than to mating. Hartwell named this point “Start”, where cells are sensitive to mating pheromones prior to reaching this stage, but insensitive to mating factors afterwards.

In the years following Hartwell’s labor-intensive experiments, it has been shown that other environmental factors contribute to cellular fate in yeast and analogously in other organisms. Though not yeast-specific, a critical study put forth by Zetterberg et al. in 1985 provided evidence for a commitment point in Swiss 3T3 cells, or mouse embryo fibroblasts, when grown in serum-rich or serum-starved conditions. Like the response to mating pheromones in Hartwell’s experiments, the response to serum starvation was not uniform amongst all cells. Only postmitotic cells younger than three hours arrested cellular division in these conditions, while cells older than four hours were insensitive to the absence of growth factors. These experimental results show strong evidence for a commitment point to enter mitosis, and consequently suggest that the cell is capable of sensing its environment for cues like growth factors before committing.

The transcription of several G1/S genes is essential for cells to proceed through the cell cycle. In budding yeast, the transcription of over 200 genes is activated at the G1/S transition. The transcription of these G1/S genes is primarily regulated by two gene regulatory proteins, SBF and MBF. These regulatory proteins form complexes with SCB and MCB, respectively, which are located on the promoters of G1/S genes.

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