Neuroprotection and repair of 3'-blocking DNA ends by glaikit (gkt) encoding Drosophila tyrosyl-DNA phosphodiesterase 1 (TDP1).
PNAS 111(44):15816 (2014)
Tyrosyl-DNA phosphodiesterase (TDP1) is a phylogenetically conserved enzyme critical for the removal of blocking lesions at the 3' ends of DNA or RNA. This study analyzes the Drosophila TDP1 gene ortholog glaikit (gkt) and its possible role(s) in the repair of endogenous DNA lesions and neuropro...
Drosophila ryanodine receptors mediate general anesthesia by halothane.
Anesthesiology 118(3):587 (2013)
Although in vitro studies have identified numerous possible targets, the molecules that mediate the in vivo effects of volatile anesthetics remain largely unknown. The mammalian ryanodine receptor (Ryr) is a known halothane target, and the authors hypothesized that it has a central role in anest...
UNC79 and UNC80, putative auxiliary subunits of the NARROW ABDOMEN ion channel, are indispensable for robust circadian locomotor rhythms in Drosophila.
PLoS ONE 8(11):e78147 (2013)
In the fruit fly Drosophila melanogaster, a network of circadian pacemaker neurons drives daily rhythms in rest and activity. The ion channel NARROW ABDOMEN (NA), orthologous to the mammalian sodium leak channel NALCN, functions downstream of the molecular circadian clock in pacemaker neurons to...
Impact of gene copy number variation on anesthesia in Drosophila melanogaster.
Anesthesiology 111(1):15 (2009)
Chromosomal deletions and duplications, which result in halving or doubling of copy number in a block of genes, are an important source of variation between individuals. Phenotypic effects of copy number variation are commonly observed, but effects on sensitivity to volatile anesthetics have not...
Genetic effects in Drosophila on the potency of diverse general anesthetics: a distinctive pattern of altered sensitivity.
Journal of Neurogenetics 23(4):412 (2009)
Mutations that influence the sensitivity of an organism to a volatile general anesthetic can be divided into two classes. In one, sensitivity to all other volatile agents is affected to a similar degree. Although this class may contain mutations of interest for understanding anesthesia, it is al...
Visual mutations reveal opposing effects of illumination on arousal in Drosophila.
Genetics 178(4):2413 (2008)
The effect of illumination on alertness can be assessed by comparing the efficacy of an anesthetic under light vs. dark conditions. Results from such tests on wild-type flies and visual mutants demonstrate that, surprisingly, light has both positive and negative influences on arousal. These dual...
Drosophila TRP channels require a protein with a distinctive motif encoded by the inaF locus.
PNAS 104(45):17730 (2007)
In both vertebrates and invertebrates, ion channels of the TRP superfamily are known to be influenced by a variety of accessory factors, but the list of interacting proteins is acknowledged to be incomplete. Although previous work showed that Drosophila TRP function is disrupted by mutations in ...
A putative cation channel and its novel regulator: cross-species conservation of effects on general anesthesia.
Current Biology 17(7):624 (2007)
Volatile anesthetics like halothane and enflurane are of interest to clinicians and neuroscientists because of their ability to preferentially disrupt higher functions that make up the conscious state. All volatiles were once thought to act identically; if so, they should be affected equally by ...
The mushroom body defect gene product is an essential component of the meiosis II spindle apparatus in Drosophila oocytes.
Genetics 173(1):243 (2006)
In addition to their well-known effects on the development of the mushroom body, mud mutants are also female sterile. Here we show that, although the early steps of ovary development are grossly normal, a defect becomes apparent in meiosis II when the two component spindles fail to cohere and al...
Retrograde signaling from the brain to the retina modulates the termination of the light response in Drosophila.
PNAS 102(49):17840 (2005)
A critical factor in visual function is the speed with which photoreceptors (PRs) return to the resting state when light intensity dims. Several elements subserve this process, many of which promote the termination of the phototransduction cascade. Although the known elements are intrinsic to PR...
The role of TDP1 from budding yeast in the repair of DNA damage.
DNA Repair 3(6):593 (2004)
The TDP1 gene encodes a protein that can hydrolyze certain types of 3'-terminal phosphodiesters, but the relevance of these catalytic activities to gene function has not been previously tested. In this work we engineered a point mutation in TDP1 and present evidence that, as per design, it sever...
A specific alteration in the electroretinogram of Drosophila melanogaster is induced by halothane and other volatile general anesthetics.
Anesthesia & Analgesia 98(6):1705 (2004)
In higher organisms, physiological investigations have provided a valuable complement to assays of anesthetic effects on whole-animal behavior. However, although complex motor programs of Drosophila melanogaster have been used to identify genes that influence anesthesia, electrophysiological stu...
An unusual cation channel mediates photic control of locomotion in Drosophila.
Current Biology 12(24):2152 (2002)
A unique family of putative ion channels that are related to voltage-gated sodium and calcium channels has been identified in genomic and cDNA studies of metazoans. Aside from evidence for expression of family members in the nervous system, little is known about the operation of the channel or i...
Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1.
PNAS 99(23):14970 (2002)
Accidental or drug-induced interruption of the breakage and reunion cycle of eukaryotic topoisomerase I (Top1) yields complexes in which the active site tyrosine of the enzyme is covalently linked to the 3' end of broken DNA. The enzyme tyrosyl-DNA phosphodiesterase (Tdp1) hydrolyzes this protei...
Crystal Structure of an IHF-DNA Complex: A Protein-Induced DNA U-Turn
Cell 87(7):1295 (1996)
Integration host factor (IHF) is a small heterodimeric protein that specifically binds to DNA and functions as an architectural factor in many cellular processes in prokaryotes. Here, we report the crystal structure of IHF complexed with 35 bp of DNA. The DNA is wrapped around the prot...