Chronobiology at the cellular and molecular levels: Models and mechanisms for circadian timekeeping

Abstract

This review considers cellular chronobiology and examines, at least in a superficial way, several classes of models and mechanisms that have been proposed for circadian rhythmicity and some of the experimental approaches that have appeared to be most productive. After a brief discussion of temporal organization and the metabolic, epigenetic, and circadian time domains, the general properties of circadian rhythms are enumerated. A survey of independent oscillations in isolated organs, tissues, and cells is followed by a review of selected circadian rhythms in eukaryotic microorganisms, with particular emphasis placed on the rhythm of cell division in the algal flagellate Euglena as a model system illustrating temporal differentiation. In the ensuing section, experimental approaches to circadian clock mechanisms are considered. The dissection of the clock by the use of chemical inhibitors is illustrated for the rhythm of bioluminescence in the marine dinoflagellate Gonyaulax and for the rhythm of photosynthetic capacity in the unicellular green alga Acetabularia. Alternatively, genetic analysis of circadian oscillators is considered in the green alga Chlamydomonas and in the bread mold Neurospora, both of which have yielded clock mutants and mutants having biochemical lesions that exhibit altered clock properties. On the basis of the evidence generated by these experimental approaches, several classes of biochemical and molecular models for circadian clocks have been proposed. These include strictly molecular models, feedback loop (network) models, transcriptional (tape-reading) models, and membrane models; some of their key elements and predictions are discussed. Finally, a number of general unsolved problems at the cellular level are briefly mentioned: cell cycle interfaces, the evolution of circadian rhythmicity, the possibility of multiple cellular oscillators, chronopharmacology and chronotherapy, and cell-cycle clocks in development and aging.

Circadian Biological Time Influences the Effect Adriamycin Has on DNA Synthesis in Mouse Bone Marrow, Ileum and Tongue but not Ehrlich Ascites Carcinoma

“…This standardization procedure does not induce rhythms, but simply synchronizes the innate, en dogenous rhythms in each individual to the environmental cue. As a result the rhythms in all variables (c.g., DNA-SA) in each animal arc entrained to the light-dark cycle and therefore the colony rhythm is identical to each individual rhythm and vice versa [6], Likewise, if a single animal is sampled serially (e.g. blood, urine, skin biopsy, etc.…”

Glyceraldehyde-3-phosphate Dehydrogenase Is Regulated on a Daily Basis by the Circadian Clock

“…Because the levels of all previously isolated N. crassa ccg genes peak in the late night to early morning corresponding to the time of day at which conidiation takes place (5-7), it has been widely assumed that the ccg genes are directly and uniquely associated with this asexual developmental pathway. This clock-regulated developmental association was viewed to be distinct from that imagined for "housekeeping genes" whose expression was expected to be relatively time-invariant; this expectation of time-invariant expression underlies the use of genes such as GAPDH 1 as loading or normalization controls. Given this, it was of particular interest in the analyses of a recent set of novel ccg genes (7) to find three ccg genes that are neither light-nor developmentally regulated.…”

“…1). These rhythms are observed in a wide variety of organisms ranging from bacteria to mammals and are coordinated with exogenous environmental cycles to limit activities at particular times of the day.…”

Expression of Circaseptan and Circannual Rhythmicity in the Imbibition of Dry Stored Bean Seeds

“…Bunning ( 11) and Edmunds (14). In previous work we showed that the rhythms observed in 9 d old etiolated bean plants met the conditions for demonstrating the endogenous character of a circadian rhythm (25).…”