Deniz Top

Deniz Top
Dalhousie University | Dal · Department of Pediatrics

About

27
Publications
3,670
Reads
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950
Citations
Citations since 2017
12 Research Items
564 Citations
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2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
Introduction
Deniz Top currently works at the Laboratory of Genetics, The Rockefeller University. Deniz does research in Genetics, Molecular Biology and Neuroscience. Their current project is 'Distinct regulatory mechanisms of local clocks'.

Publications

Publications (27)
Article
Circadian clocks are self-sustained molecular oscillators controlling daily changes of behavioral activity and physiology. For functional reliability and precision, the frequency of these molecular oscillations must be stable at different environmental temperatures, known as "temperature compensation." Despite being an intrinsic property of all cir...
Article
Full-text available
Circadian clocks are highly conserved transcriptional regulators that control ~24-hour oscillations in gene expression, physiological function, and behavior. Circadian clocks exist in almost every tissue and are thought to control tissue-specific gene expression and function, synchronized by the brain clock. Many disease states are associated with...
Preprint
Full-text available
Circadian clocks are highly conserved transcriptional regulators that control 24-hour oscillations in gene expression, physiological function, and behavior. Circadian clocks exist in almost every tissue and are thought to control tissue-specific gene expression and function, synchronized by the brain clock. Many disease states are associated with l...
Preprint
Full-text available
Circadian clocks are self-sustained molecular oscillators controlling daily changes of behavioral activity and physiology. For functional reliability and precision the frequency of these molecular oscillations must be stable at different environmental temperatures, known as ‘temperature compensation’. Despite being an intrinsic property of all circ...
Article
Full-text available
Defects in histone methyltransferases (HMTs) are major contributing factors in neurodevelopmental disorders (NDDs). Heterozygous variants of SETD1A involved in histone H3 lysine 4 (H3K4) methylation were previously identified in individuals with schizophrenia. Here, we define the clinical features of the Mendelian syndrome associated with haploinsu...
Article
Full-text available
Circadian clocks are biochemical time-keeping machines that synchronize animal behavior and physiology with planetary rhythms. In Drosophila, the core components of the clock comprise a transcription/translation feedback loop and are expressed in seven neuronal clusters in the brain. Although it is increasingly evident that the clocks in each of th...
Preprint
Full-text available
Defects in histone methyltransferases (HMTs) are major contributing factors in neurodevelopmental disorders (NDDs). Heterozygous variants of SETD1A involved in histone H3 lysine 4 (H3K4) methylation were previously identified in individuals with schizophrenia. Here, we define the clinical features of the Mendelian syndrome associated with haploinsu...
Article
Full-text available
In theDrosophilacircadian clock, Period (PER) and Timeless (TIM) proteins inhibit Clock-mediated transcription ofperandtimgenes until PER is degraded by Doubletime/CK1 (DBT)-mediated phosphorylation, establishing a negative feedback loop. Multiple regulatory delays within this feedback loop ensure ~24 hr periodicity. Of these delays, the mechanisms...
Data
Fly behavioral data. Behavioral periods of flies charted in Figure 1B, C and D are detailed. Tau: behavioral period, SD: standard deviation, No. Arr.: Number of arrhythmic flies, Total Number: Total number of flies tested. fs: figure supplement.
Article
Significance This work resolves a long-standing controversy regarding the activation mechanism and photocycle of cryptochromes (CRYs), a broadly represented group of photosensors. We demonstrate a high degree of correspondence between the capability of the tryptophan (Trp) chain to photoreduce the flavin cofactor and biological activity. These resu...
Article
Specialized groups of neurons in the brain are key mediators of circadian rhythms, receiving daily environmental cues and communicating those signals to other tissues in the organism for entrainment and to organize circadian physiology. In Drosophila, the "circadian clock" is housed in seven neuronal clusters, which are defined by their expression...
Article
Significance There are few detailed mechanistic models that describe how light-sensing proteins convert photochemistry into conformational signals. Combined computational and experimental investigations reveal how photoreduction of the Drosophila cryptochrome (dCRY) flavin induces protonation of a neighboring conserved His residue. Altered His hydr...
Article
Full-text available
The molecular clock relies on a delayed negative feedback loop of transcriptional regulation to generate oscillating gene expression. Although the principal components of the clock are present in all circadian neurons, different neuronal clusters have varying effects on rhythmic behavior, suggesting that the clocks they house are differently regula...
Article
Full-text available
Significance Cryptochromes (CRYs) are photosensors that play central roles in the circadian rhythms of plants and animals. CRYs are related to photolyase DNA-repair enzymes, but instead of binding DNA, insect CRYs bind a C-terminal tail (CTT) α-helix in the pocket that holds the light-sensing flavin molecule. There is no consensus on how light acti...
Article
Full-text available
The p15 fusion-associated small transmembrane (FAST) protein is a nonstructural viral protein that induces cell-cell fusion and syncytium formation. The exceptionally small, myristoylated N-terminal ectodomain of p15 lacks any of the defining features of a typical viral fusion protein. NMR and CD spectroscopy indicate this small fusion module compr...
Article
Full-text available
The cryptochrome/photolyase (CRY/PL) family of photoreceptors mediates adaptive responses to ultraviolet and blue light exposure in all kingdoms of life. Whereas PLs function predominantly in DNA repair of cyclobutane pyrimidine dimers (CPDs) and 6-4 photolesions caused by ultraviolet radiation, CRYs transduce signals important for growth, developm...
Article
Full-text available
The reovirus fusion-associated small transmembrane (FAST) proteins are virus-encoded membrane fusion proteins that function as dedicated cell-cell fusogens. The topology of these small, single-pass membrane proteins orients the majority of the protein on the distal side of the membrane (i.e., inside the cell). We now show that ectopic expression of...
Article
Full-text available
The reovirus fusion-associated small transmembrane (FAST) proteins function as virus-encoded cellular fusogens, mediating efficient cell-cell rather than virus-cell membrane fusion. With ectodomains of only approximately 20-40 residues, it is unclear how such diminutive viral fusion proteins mediate the initial stages (i.e. membrane contact and clo...
Article
Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide that kills Jurkat T-leukemia cells by the mitochondrial pathway of apoptosis. However, the process by which LfcinB triggers mitochondria-dependent apoptosis is not well understood. Here, we show that LfcinB-induced apoptosis in Jurkat T-leukemia cells was preceded by LfcinB binding t...
Article
Full-text available
Biological membrane fusion is dependent on protein catalysts to mediate localized restructuring of lipid bilayers. A central theme in current models of protein-mediated membrane fusion involves the sequential refolding of complex homomeric or heteromeric protein fusion machines. The structural features of a new family of fusion-associated small tra...
Article
Full-text available
The fusion-associated small transmembrane (FAST) proteins of the fusogenic reoviruses are the only known examples of membrane fusion proteins encoded by non-enveloped viruses. While the involvement of the FAST proteins in mediating extensive syncytium formation in virus-infected and -transfected cells is well established, the nature of the fusion r...
Article
Full-text available
Members of the fusion-associated small transmembrane (FAST) protein family are a distinct class of membrane fusion proteins encoded by nonenveloped fusogenic reoviruses. The 125-residue p14 FAST protein of reptilian reovirus has an approximately 38-residue myristoylated N-terminal ectodomain containing a moderately apolar N-proximal region, termed...

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Projects

Project (1)
Project
To identify the regulatory mechanisms in localized tissues