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Citation
Saez, L., Derasmo, M., Meyer, P., Stieglitz, J., Young, M.W. (2011). A key temporal delay in the circadian cycle of Drosophila is mediated by a nuclear localization signal in the timeless protein.  Genetics 188(3): 591--600.
FlyBase ID
FBrf0214282
Publication Type
Research paper
Abstract

Regulated nuclear entry of the Period (PER) and Timeless (TIM) proteins, two components of the Drosophila circadian clock, is essential for the generation and maintenance of circadian behavior. PER and TIM shift from the cytoplasm to the nucleus daily, and the length of time that PER and TIM reside in the cytoplasm is an important determinant of the period length of the circadian rhythm. Here we identify a TIM nuclear localization signal (NLS) that is required for appropriately timed nuclear accumulation of both TIM and PER. Transgenic flies with a mutated TIM NLS produced circadian rhythms with a period of ∼30 hr. In pacemaker cells of the brain, PER and TIM proteins rise to abnormally high levels in the cytoplasm of tim(ΔNLS) mutants, but show substantially reduced nuclear accumulation. In cultured S2 cells, the mutant TIM(ΔNLS) protein significantly delays nuclear accumulation of both TIM and wild-type PER proteins. These studies confirm that TIM is required for the nuclear localization of PER and point to a key role for the TIM NLS in the regulated nuclear accumulation of both proteins.

PubMed ID
PubMed Central ID
PMC3176546 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genetics
    Title
    Genetics
    Publication Year
    1916-
    ISBN/ISSN
    0016-6731
    Data From Reference
    Alleles (4)
    Genes (2)
    Physical Interactions (1)
    Cell Lines (2)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (2)