Cellular signalling and the complexity of biological timing: insights from the ultradian clock ofSchizosaccharomyces pombe

Abstract

The molecular bases of circadian clocks are complex and cannot be sufficiently explained by the relatively simple feedback loops, based on transcription and translation, of current models. The existence of additional oscillators has been demonstrated experimentally, but their mechanism(s) have so far resisted elucidation and any universally conserved clock components have yet to be identified. The fission yeast,Schizosaccharomyces pombe, as a simple and well–characterized eukaryote, is a useful model organism in the investigation of many aspects of cell regulation. In fast–growing cells of the yeast an ultradian clock operates, which can serve as a model system to analyse clock complexity. This clock shares strict period homeostasis and efficient entrainment with circadian clocks but, because of its short period of 30 min, mechanisms other than a transcription/translation–based feedback loop must be working. An initial systematic screen involving over 200 deletion mutants has shown that major cellular signalling pathways (calcium/phosphoinositide, mitogen–activated protein kinase and cAMP/protein kinase A) are crucial for the normal functioning of this ultradian clock. A comparative examination of the role of cellular signalling pathways in theS.pombeultradian clock and in the circadian timekeeping of different eukaryotes may indicate common principles in biological timing processes that are universally conserved amongst eukaryotes.