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

Adrian Rothenfluh, Michael W. Young, Lino Saez

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


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 languageEnglish (US)
Pages (from-to)505-514
Number of pages10
Issue number2
StatePublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)


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