A TIMELESS-independent function for PERIOD proteins in the Drosophila clock

Adrian Rothenfluh; Michael W. Young; Lino Saez

doi:10.1016/S0896-6273(00)81182-4

A TIMELESS-independent function for PERIOD proteins in the Drosophila clock

Adrian Rothenfluh, Michael W. Young, Lino Saez

Research output: Contribution to journal › Article › peer-review

133 Scopus citations

Abstract

The mutation timeless(UL) generates 33 hr rhythms, prolonged nuclear localization of PERIOD/TIMELESS(UL) protein complexes, and protracted derepression of period (per) and timeless (tim) transcription. Light-induced elimination of TIM(UL) from nuclear PER/TIM(UL) complexes gives strong downregulation of per and tim expression. Thus, in the absence of TIM, nuclear PER can function as a potent negative transcriptional regulator. Two additional studies support this role for PER: (1) Drosophila expressing PER that constitutively localizes to nuclei produce dominant behavioral arrhythmicity, and (2) constitutively nuclear PER represses dCLOCK/CYCLE-mediated transcription of per in cultured cells without TIM. Conversion of PER/TIM heterodimers to nuclear PER proteins appears to be required to complete transcriptional repression and terminate each circadian molecular cycle.

Original language	English (US)
Pages (from-to)	505-514
Number of pages	10
Journal	Neuron
Volume	26
Issue number	2
DOIs	https://doi.org/10.1016/S0896-6273(00)81182-4
State	Published - 2000

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/S0896-6273(00)81182-4

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@article{0e7a8d9576824332938bf7789d5a817e,

title = "A TIMELESS-independent function for PERIOD proteins in the Drosophila clock",

abstract = "The mutation timeless(UL) generates 33 hr rhythms, prolonged nuclear localization of PERIOD/TIMELESS(UL) protein complexes, and protracted derepression of period (per) and timeless (tim) transcription. Light-induced elimination of TIM(UL) from nuclear PER/TIM(UL) complexes gives strong downregulation of per and tim expression. Thus, in the absence of TIM, nuclear PER can function as a potent negative transcriptional regulator. Two additional studies support this role for PER: (1) Drosophila expressing PER that constitutively localizes to nuclei produce dominant behavioral arrhythmicity, and (2) constitutively nuclear PER represses dCLOCK/CYCLE-mediated transcription of per in cultured cells without TIM. Conversion of PER/TIM heterodimers to nuclear PER proteins appears to be required to complete transcriptional repression and terminate each circadian molecular cycle.",

author = "Adrian Rothenfluh and Young, {Michael W.} and Lino Saez",

note = "Funding Information: We are very grateful to Marla Abodeely for her excellent technical assistance at many stages of the project. We thank Jeff Price and Evelyn Icasiano for their help during the genetic screen. We thank Ralf Stanewsky and Jeff Hall for anti-PER antibody, and Tom Darlington and Steve Kay for sharing materials and data prior to publication. We also thank Jeff Hall and Brian Kloss for valuable suggestions, and, especially, Justin Blau and Cedric Wesley for many helpful discussions, critical reading of the manuscript, and help in generating the P element lines. A. R. was supported by a Beckman fellowship. This work was supported by National Institutes of Health grant GM-54339 and the National Science Foundation Science and Technology Center for Biological Timing (M. W. Y.).",

year = "2000",

doi = "10.1016/S0896-6273(00)81182-4",

language = "English (US)",

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AU - Rothenfluh, Adrian

AU - Young, Michael W.

AU - Saez, Lino

N1 - Funding Information: We are very grateful to Marla Abodeely for her excellent technical assistance at many stages of the project. We thank Jeff Price and Evelyn Icasiano for their help during the genetic screen. We thank Ralf Stanewsky and Jeff Hall for anti-PER antibody, and Tom Darlington and Steve Kay for sharing materials and data prior to publication. We also thank Jeff Hall and Brian Kloss for valuable suggestions, and, especially, Justin Blau and Cedric Wesley for many helpful discussions, critical reading of the manuscript, and help in generating the P element lines. A. R. was supported by a Beckman fellowship. This work was supported by National Institutes of Health grant GM-54339 and the National Science Foundation Science and Technology Center for Biological Timing (M. W. Y.).

PY - 2000

Y1 - 2000

N2 - The mutation timeless(UL) generates 33 hr rhythms, prolonged nuclear localization of PERIOD/TIMELESS(UL) protein complexes, and protracted derepression of period (per) and timeless (tim) transcription. Light-induced elimination of TIM(UL) from nuclear PER/TIM(UL) complexes gives strong downregulation of per and tim expression. Thus, in the absence of TIM, nuclear PER can function as a potent negative transcriptional regulator. Two additional studies support this role for PER: (1) Drosophila expressing PER that constitutively localizes to nuclei produce dominant behavioral arrhythmicity, and (2) constitutively nuclear PER represses dCLOCK/CYCLE-mediated transcription of per in cultured cells without TIM. Conversion of PER/TIM heterodimers to nuclear PER proteins appears to be required to complete transcriptional repression and terminate each circadian molecular cycle.

AB - The mutation timeless(UL) generates 33 hr rhythms, prolonged nuclear localization of PERIOD/TIMELESS(UL) protein complexes, and protracted derepression of period (per) and timeless (tim) transcription. Light-induced elimination of TIM(UL) from nuclear PER/TIM(UL) complexes gives strong downregulation of per and tim expression. Thus, in the absence of TIM, nuclear PER can function as a potent negative transcriptional regulator. Two additional studies support this role for PER: (1) Drosophila expressing PER that constitutively localizes to nuclei produce dominant behavioral arrhythmicity, and (2) constitutively nuclear PER represses dCLOCK/CYCLE-mediated transcription of per in cultured cells without TIM. Conversion of PER/TIM heterodimers to nuclear PER proteins appears to be required to complete transcriptional repression and terminate each circadian molecular cycle.

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A TIMELESS-independent function for PERIOD proteins in the Drosophila clock

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