Cellular signalling and the complexity of biological timing: insights fromthe ultradian clock of Schizosaccharomyces pombe

The molecular bases of circadian clocks are complex and cannot be sufficien tly explained by the relatively simple feedback loops, based on transcripti on and translation, of current models. The existence of additional oscillat ors has been demonstrated experimentally, but their mechanism(s) have so fa r resisted elucidation and any universally conserved clock components have vet to be identified. The fission yeast, Schizosoccharomyces pombe., as a s imple and well-characterized eukaryote, is a useful model organism in the i nvestigation of many aspects of cell regulation. In fast-growing cells of t he yeast an ultradian clock operate:, which can serve as a model system to analyse clock complexity. This clock shares strict period homeostasis and e fficient entrainment with circadian clocks but, because of its :short perio d of 30 min, mechanisms other than a transcription/ translation-based feedb ack loop must be working. An initial systematic screen involving over 200 d eletion mutants has shown that major cellular signalling pathways calcium/p hosphoinositide, mitogen-activated protein kinase and cAMP/protein kinase A ) are crucial for the normal functioning of this ultradian clock. A compara tive examination of the role of cellular signalling pathways in the S. pomb e ultradian clock and in the circadian timekeeping of different eukaryotes may indicate common principles in biological timing processes that are univ ersally conserved amongst eukaryotes.