A second timeless gene in Drosophila shares greater sequence similarity with mammalian tim

Benna, Clara; Scannapieco, Paolo; Piccin, Alberto; Sandrelli, Federica; Zordan, Mauro Agostino; Rosato, Ezio; Kyriacou, C. P.; Valle, Giorgio; Costa, Rodolfo

doi:10.1016/s0960-9822(00)00594-7

Cited by 75 publications

(54 citation statements)

References 10 publications

(12 reference statements)

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“…TIMELESS belongs to a protein family that includes a second Drosophila protein, dTIMEOUT, or dTIM2, which is homologous to mouse (mTIM) and Caenorhabditis elegans (ceTIM-1) proteins involved in development (11,12,23). However, apTIM is more closely related to dTIM than to dTIMEOUT (11,12), indicating that it is an ortholog of dTIM, rather than of dTIMEOUT.…”

Section: Resultsmentioning

confidence: 99%

“…It is absent from C. elegans, humans, puffer fish (Fugu rubripes), and sea squirt (Ciona intestinalis), four animals whose genomes have been almost completely sequenced (39 -43). timeout-like genes, on the other hand, are found universally in animals, suggesting that timeless evolved from a gene duplication of timeout, perhaps in the arthropod lineage (12). timeless orthologs have been cloned from a number of dipterans, including Drosophila species (44,45), the drosophilid fruit fly Chymomyza costata (GenBank TM number BAB91179), and the non-drosophilid fly Sarcophaga crassipalpis (46).…”

Section: Table II Subcellular Localization Of V5-tagged Apper Constructsmentioning

confidence: 99%

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Constructing a Feedback Loop with Circadian Clock Molecules from the Silkmoth, Antheraea pernyi

Chang

McWatters

Williams

et al. 2003

Journal of Biological Chemistry

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Circadian clocks are important regulators of behavior and physiology. The circadian clock of Drosophila depends on an autoinhibitory feedback loop involving dCLOCK, CYCLE (also called dBMAL, for Drosophila brain and muscle ARNT-like protein), dPERIOD, and dTIMELESS. Recent studies suggest that the clock mechanism in other insect species may differ strikingly from that of Drosophila. We cloned Clock, Bmal, and Timeless homologs (apClock, apBmal, and apTimeless) from the silkmoth Antheraea pernyi, from which a Period homolog (apPeriod) has already been cloned. In Schneider 2 (S2) cell culture assays, apCLOCK:apBMAL activates transcription through an E-box enhancer element found in the 5 region of the apPeriod gene. Furthermore, apPERIOD can robustly inhibit apCLOCK: apBMAL-mediated transactivation, and apTIMELESS can augment this inhibition. Thus, a complete feedback loop, resembling that found in Drosophila, can be constructed from silkmoth CLOCK, BMAL, PERIOD, and TIMELESS. Our results suggest that the circadian autoinhibitory feedback loop discovered in Drosophila is likely to be widespread among insects. However, whereas the transactivation domain in Drosophila lies in the C terminus of dCLOCK, in A. pernyi, it lies in the C terminus of apBMAL, which is highly conserved with the C termini of BMALs in other insects (except Drosophila) and in vertebrates. Our analysis sheds light on the molecular function and evolution of clock genes in the animal kingdom.

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Section: Resultsmentioning

confidence: 99%

Section: Table II Subcellular Localization Of V5-tagged Apper Constructsmentioning

confidence: 99%

Constructing a Feedback Loop with Circadian Clock Molecules from the Silkmoth, Antheraea pernyi

Chang

McWatters

Williams

et al. 2003

Journal of Biological Chemistry

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“…Orthologs have been found in several species including mammals and Caenorhabditis elegans (2)(3)(4). A structurally related paralog in Drosophila, Timeout, has been identified (5). This is an essential gene in mice (6).…”

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confidence: 99%

Tipin and Timeless form a mutually protective complex required for genotoxic stress resistance and checkpoint function

Chou

Elledge²

2006

Proc. Natl. Acad. Sci. U.S.A.

152

151

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Tipin is a mammalian protein that interacts with Timeless, which plays a role in DNA damage checkpoint responses. Here, we show that Tipin is a nuclear protein that associates with the replicative helicase and protects cells against genotoxic agents. Tipin is required for efficient cell cycle arrest in response to DNA damage, and depletion of Tipin renders cells sensitive to ionizing radiation as well as replication stress. Loss of Tipin results in spontaneous ␥-H2AX foci, a marker for DNA double-strand breaks. We find that Tipin and Timeless form a complex that maintains the level of both proteins in cells and that the loss of either one will lead to the loss of the interacting partner. This observation explains the similar checkpoint phenotypes observed in both Tipin-and Timeless-depleted cells.DNA damage ͉ S phase ͉ cell cycle control ͉ circadian rhythms

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“…Although it is not yet clear whether tim2 has a circadian function in the fly, this sequence is more closely related to the single mammalian tim sequence, than is fly tim. 87,88 Thus, tim2 must be the ancestral sequence, which in diptera and lepidoptera, at least, has relatively recently duplicated to generate the clock-relevant tim. A role for mTim in the mammalian clock has been proposed from the work of Barnes et al 89 and Ü nsal-Kac¸maz et al, 90 the latter suggesting that the role of mammalian TIM is to couple the circadian clock to the cell cycle.…”

Section: How the Clock Responds To Lightmentioning

confidence: 99%

Molecular genetics of the fruit-fly circadian clock

2006

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The circadian clock percolates through every aspect of behaviour and physiology, and has wide implications for human and animal health. The molecular basis of the Drosophila circadian clock provides a model system that has remarkable similarities to that of mammals. The various cardinal clock molecules in the fly are outlined, and compared to those of their actual and 'functional' homologues in the mammal. We also focus on the evolutionary tinkering of these clock genes and compare and contrast the neuronal basis for behavioural rhythms between the two phyla.

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A second timeless gene in Drosophila shares greater sequence similarity with mammalian tim

Cited by 75 publications

References 10 publications

Constructing a Feedback Loop with Circadian Clock Molecules from the Silkmoth, Antheraea pernyi

Constructing a Feedback Loop with Circadian Clock Molecules from the Silkmoth, Antheraea pernyi

Tipin and Timeless form a mutually protective complex required for genotoxic stress resistance and checkpoint function

Molecular genetics of the fruit-fly circadian clock

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