Nuclear localization and transcriptional repression are confined to separable domains in the circadian protein CRYPTOCHROME

Haisun Zhu, Francesca Conte, Carla B. Green

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Circadian rhythms are driven by molecular clocks composed of interlocking transcription/translation feedback loops [1, 2]. CRYPTOCHROME (CRY) proteins are critical components of these clocks [3, 4] and repress the activity of the transcription factor heterodimer CLOCK/BMAL1 [5-7]. Unlike the homologous DNA repair enzyme 6-4 PHOTOLYASE, CRYs have extended carboxyl-terminal tails and cannot repair DNA damage (reviewed in [8]). Unlike mammals, Xenopus laevis contains both CRYs (xCRYs) and 6-4 PHOTOLYASE (xPHOTOLYASE), providing an excellent comparative tool to study CRY repressive function. We can extend findings to CRYs in general because xCRYs share high sequence homology with mammalian CRYs [9]. We show here that deletion of xCRYs' C-terminal domain produces proteins that are, like xPHOTOLYASE, unable to suppress CLOCK/BMAL1 activation. However, these truncations also cause the proteins to be cytoplasmically localized. A heterologous nuclear localization signal (NLS) restores the truncation mutants' nuclear localization and repressive activity. Our results demonstrate that the CRYs' C termini are essential for nuclear localization but not necessary for the suppression of CLOCK/BMAL1 activation; this finding indicates that these two functions reside in separable domains. Furthermore, the functional differences between CRYs and PHOTOLYASE can be attributed to the few amino acid changes in the conserved portions of these proteins.

Original languageEnglish (US)
Pages (from-to)1653-1656
Number of pages4
JournalCurrent Biology
Volume13
Issue number18
DOIs
StatePublished - Sep 16 2003

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DNA Repair Enzymes
Clocks
Nuclear Localization Signals
Proteins
proteins
Chemical activation
Xenopus laevis
Sequence Homology
Circadian Rhythm
nuclear localization signals
DNA Damage
Mammals
Tail
Transcription Factors
Transcription
DNA repair
sequence homology
DNA damage
circadian rhythm
translation (genetics)

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Nuclear localization and transcriptional repression are confined to separable domains in the circadian protein CRYPTOCHROME. / Zhu, Haisun; Conte, Francesca; Green, Carla B.

In: Current Biology, Vol. 13, No. 18, 16.09.2003, p. 1653-1656.

Research output: Contribution to journalArticle

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