A simple model of circadian rhythms based on dimerization and proteolysis of PER and TIM

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dc.contributor.authorTyson, John J.en
dc.contributor.authorHong, Christian I.en
dc.contributor.authorThron, C. Dennisen
dc.contributor.authorNovak, Belaen
dc.contributor.departmentBiological Sciencesen
dc.date.accessed2014-02-05en
dc.date.accessioned2014-02-26T19:10:04Zen
dc.date.available2014-02-26T19:10:04Zen
dc.date.issued1999-11en
dc.description.abstractMany organisms display rhythms of physiology and behavior that are entrained to the 24-h cycle of light and darkness prevailing on Earth. Under constant conditions of illumination and temperature, these internal biological rhythms persist with a period close to 1 day("circadian"), but it is usually not exactly 24 h. Recent discoveries have uncovered stunning similarities among the molecular circuitries of circadian clocks in mice, fruit flies, and bread molds. A consensus picture is coming into focus around two proteins (called PER and TIM in fruit flies), which dimerize and then inhibit transcription of their own genes. Although this picture seems to confirm a venerable model of circadian rhythms based on time-delayed negative feedback, we suggest that just as crucial to the circadian oscillator is a positive feedback loop based on stabilization of PER upon dimerization. These ideas can be expressed in simple mathematical form(phase plane portraits), and the model accounts naturally for several hallmarks of circadian rhythms, including temperature compensation and the per(L) mutant phenotype. In addition, the model suggests how an endogenous circadian oscillator could have evolved from a more primitive, light-activated switch.en
dc.description.sponsorshipHoward Hughes Medical Institute 75195-512302en
dc.description.sponsorshipNational Science Foundation DMS-9525766en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationTyson, JJ; Hong, CI; Thron, CD; et al., "A simple model of circadian rhythms based on dimerization and proteolysis of PER and TIM," Biophysical Journal 77(5), 2411-2417 (1999); doi: 10.1016/s0006-3495(99)77078-5en
dc.identifier.doihttps://doi.org/10.1016/s0006-3495(99)77078-5en
dc.identifier.issn0006-3495en
dc.identifier.urihttp://hdl.handle.net/10919/25768en
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0006349599770785#en
dc.language.isoenen
dc.publisherCELL PRESSen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectdrosophila clock geneen
dc.subjecttemperature-compensationen
dc.subjectperiod proteinen
dc.subjecttimelessen
dc.subjecttranscriptionen
dc.subjectfeedbacken
dc.subjectLighten
dc.subjectmelanogasteren
dc.subjectoscillationsen
dc.subjectentrainmenten
dc.titleA simple model of circadian rhythms based on dimerization and proteolysis of PER and TIMen
dc.title.serialBiophysical Journalen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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