Abstract

Most cells must grow before they can divide, but it is not known how cells determine when they have grown enough so they can commit to a new round of cell division. Several parameters affect the timing of initiation of division: cell size at birth, the size cells have to reach when they commit to division, and how fast they reach that size. We report that Saccharomyces cerevisiae mutants in metabolic and biosynthetic pathways differ in these variables, controlling the timing of initiation of cell division in various ways. Some mutants affect the size at birth, size at initiation of division, the rate of increase in size, or any combination of the above. Furthermore, we show that adenylate kinase, encoded by ADK1, is a significant determinant of the efficiency of size control mechanisms. Finally, our data argue strongly that the cell size at division is not necessarily a function of the rate cells increase in size in the G1 phase of the cell cycle. Taken together, these findings reveal an unexpected diversity in the G1 cell cycle phenotypes of metabolic and biosynthetic mutants, suggesting that growth requirements for cell division are multiple, distinct and imposed throughout the G1 phase of the cell cycle.

Highlights

  • In proliferating cells, the G1 phase of any given cell cycle lasts from the end of the previous mitosis until the beginning of DNA synthesis

  • The kinase Tda1p contributes to the control of the rate of size increase in response to carbon source To examine further the relationship between the rate of size increase and critical size, we focused on Tda1p because we had previously shown that cells lacking Tda1p

  • We discuss our results in the context of previous reports linking critical size with the rate of size increase, and we expand on the implications of our findings in regard with the cell cycle phenotypes of the mutants we examined

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Summary

Introduction

The G1 phase of any given cell cycle lasts from the end of the previous mitosis until the beginning of DNA synthesis. Differences in the length of G1 account for most of the differences in total cell cycle, or generation times, between the same cells growing in different media [1,2,3,4,5,6] It is not clear how cells determine what growth requirements have to be met and how they are monitored so that cells can commit to a new round of cell division, at a point in late G1 called START. Mutations in essential metabolic genes that arrest cell division at or before START have not received much attention Such mutants were thought to resemble nutritionally limited cells because their growth in size was inhibited [6, 7]. Metabolic requirements for division may be multiple, distinct and imposed at different times from cell birth until commitment to a new round of cell division at START

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