Heat-Induced Calcium Leakage Causes Mitochondrial Damage in Caenorhabditis elegans Body-Wall Muscles [Developmental and Behavioral Genetics]
Acute onset of organ failure in heatstroke is triggered by rhabdomyolysis of skeletal muscle. Here, we showed that elevated temperature increases free cytosolic Ca2+ [Ca2+]f from RYR (ryanodine receptor)/UNC-68 in vivo in the muscles of an experimental model animal, the nematode Caenorhabditis elegans. This subsequently leads to mitochondrial fragmentation and dysfunction, and breakdown of myofilaments similar to rhabdomyolysis. In addition, treatment with an inhibitor of RYR (dantrolene) or activation of FoxO (Forkhead box O)/DAF-16 is effective against heat-induced muscle damage. Acute onset of organ failure in heatstrok...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Momma, K., Homma, T., Isaka, R., Sudevan, S., Higashitani, A. Tags: Developmental and Behavioral Genetics Source Type: research
Genomic Analysis of Genotype-by-Social Environment Interaction for Drosophila melanogaster Aggressive Behavior [Developmental and Behavioral Genetics]
Human psychiatric disorders such as schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder often include adverse behaviors including increased aggressiveness. Individuals with psychiatric disorders often exhibit social withdrawal, which can further increase the probability of conducting a violent act. Here, we used the inbred, sequenced lines of the Drosophila Genetic Reference Panel (DGRP) to investigate the genetic basis of variation in male aggressive behavior for flies reared in a socialized and socially isolated environment. We identified genetic variation for aggressive behavior, as well as sig...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Rohde, P. D., Gaertner, B., Ward, K., Sorensen, P., Mackay, T. F. C. Tags: Developmental and Behavioral Genetics Source Type: research
Coordination of Heparan Sulfate Proteoglycans with Wnt Signaling To Control Cellular Migrations and Positioning in Caenorhabditis elegans [Developmental and Behavioral Genetics]
Heparan sulfates (HS) are linear polysaccharides with complex modification patterns, which are covalently bound via conserved attachment sites to core proteins to form heparan sulfate proteoglycans (HSPGs). HSPGs regulate many aspects of the development and function of the nervous system, including cell migration, morphology, and network connectivity. HSPGs function as cofactors for multiple signaling pathways, including the Wnt-signaling molecules and their Frizzled receptors. To investigate the functional interactions among the HSPG and Wnt networks, we conducted genetic analyses of each, and also between these networks ...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Saied-Santiago, K., Townley, R. A., Attonito, J. D., da Cunha, D. S., Diaz-Balzac, C. A., Tecle, E., Bulow, H. E. Tags: Developmental and Behavioral Genetics Source Type: research
Control of a Novel Spermatocyte-Promoting Factor by the Male Germline Sex Determination Factor PHF7 of Drosophila melanogaster [Developmental and Behavioral Genetics]
A key aspect of germ cell development is to establish germline sexual identity and initiate a sex-specific developmental program to promote spermatogenesis or oogenesis. Previously, we have identified the histone reader Plant Homeodomain Finger 7 (PHF7) as an important regulator of male germline identity. To understand how PHF7 directs sexual differentiation of the male germline, we investigated the downstream targets of PHF7 by combining transcriptome analyses, which reveal genes regulated by Phf7, with genomic profiling of histone H3K4me2, the chromatin mark that is bound by PHF7. Through these genomic experiments, we id...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Yang, S. Y., Chang, Y.-C., Wan, Y. H., Whitworth, C., Baxter, E. M., Primus, S., Pi, H., Van Doren, M. Tags: Developmental and Behavioral Genetics Source Type: research
Shrinking Daughters: Rlm1-Dependent G1/S Checkpoint Maintains Saccharomyces cerevisiae Daughter Cell Size and Viability [Cellular Genetics]
We report that an rlm1 mutant grown on a nonfermentable carbon source at low osmolarity forms cell groups in which a mother cell is surrounded by smaller "satellite-daughter" cells. Mother cells in these groups progressed through repeated rounds of cell division with normal rates of bud growth and genetic stability; however, these cells underwent precocious START relative to wild-type mothers. Thus, once activated, Rlm1 delays the transition from G1 to S, a mechanism we term the cell wall/START (CW/START) checkpoint. The rlm1 satellite-cell phenotype is suppressed by deletion of either SLT2, which encodes the kinase that a...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Piccirillo, S., Neog, D., Spade, D., Van Horn, J. D., Tiede-Lewis, L. M., Dallas, S. L., Kapros, T., Honigberg, S. M. Tags: Cellular Genetics Source Type: research
The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2 [Cellular Genetics]
Cellular damage caused by reactive oxygen species is believed to be a major contributor to age-associated diseases. Previously, we characterized the Caenorhabditis elegans Brap2 ortholog (BRAP-2) and found that it is required to prevent larval arrest in response to elevated levels of oxidative stress. Here, we report that C. elegans brap-2 mutants display increased expression of SKN-1-dependent, phase II detoxification enzymes that is dependent on PMK-1 (a p38 MAPK C. elegans ortholog). An RNA-interference screen was conducted using a transcription factor library to identify genes required for increased expression of the S...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Hu, Q., DAmora, D. R., MacNeil, L. T., Walhout, A. J. M., Kubiseski, T. J. Tags: Cellular Genetics Source Type: research
Epigenetic Transcriptional Memory of GAL Genes Depends on Growth in Glucose and the Tup1 Transcription Factor in Saccharomyces cerevisiae [Gene Expression]
Previously expressed inducible genes can remain poised for faster reactivation for multiple cell divisions, a conserved phenomenon called epigenetic transcriptional memory. The GAL genes in Saccharomyces cerevisiae show faster reactivation for up to seven generations after being repressed. During memory, previously produced Gal1 protein enhances the rate of reactivation of GAL1, GAL10, GAL2, and GAL7. These genes also interact with the nuclear pore complex (NPC) and localize to the nuclear periphery both when active and during memory. Peripheral localization of GAL1 during memory requires the Gal1 protein, a memory-specifi...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Sood, V., Cajigas, I., DUrso, A., Light, W. H., Brickner, J. H. Tags: Gene Expression Source Type: research
Up-Frameshift Protein UPF1 Regulates Neurospora crassa Circadian and Diurnal Growth Rhythms [Gene Expression]
In this study, we report that in the filamentous fungus Neurospora crassa, the NMD factors play a conserved role in regulating the surveillance of NMD targets including premature termination codon (PTC)-containing transcripts and normal transcripts. The circadian rhythms in all of the knockout strains of upf1-3 genes, which encode the Up-frameshift proteins, were aberrant. The upf1 knockout strain displays a shortened circadian period, which can be restored by constantly expressing exogenous Up-frameshift protein 1 (UPF1). UPF1 regulates the circadian clock by modulating the splicing of the core clock gene frequency (frq) ...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Wu, Y., Zhang, Y., Sun, Y., Yu, J., Wang, P., Ma, H., Chen, S., Ma, L., Zhang, D., He, Q., Guo, J. Tags: Gene Expression Source Type: research
Evolving Mistranslating tRNAs Through a Phenotypically Ambivalent Intermediate in Saccharomyces cerevisiae [Gene Expression]
The genetic code converts information from nucleic acid into protein. The genetic code was thought to be immutable, yet many examples in nature indicate that variations to the code provide a selective advantage. We used a sensitive selection system involving suppression of a deleterious allele (tti2-L187P) in Saccharomyces cerevisiae to detect mistranslation and identify mechanisms that allow genetic code evolution. Though tRNASer containing a proline anticodon (UGG) is toxic, using our selection system we identified four tRNASer UGG variants, each with a single mutation, that mistranslate at a tolerable level. Mistranslat...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Berg, M. D., Hoffman, K. S., Genereaux, J., Mian, S., Trussler, R. S., Haniford, D. B., ODonoghue, P., Brandl, C. J. Tags: Gene Expression Source Type: research
A Role for the Nonsense-Mediated mRNA Decay Pathway in Maintaining Genome Stability in Caenorhabditis elegans [Genome Integrity and Transmission]
Ionizing radiation (IR) is commonly used in cancer therapy and is a main source of DNA double-strand breaks (DSBs), one of the most toxic forms of DNA damage. We have used Caenorhabditis elegans as an invertebrate model to identify novel factors required for repair of DNA damage inflicted by IR. We have performed an unbiased genetic screen, finding that smg-1 mutations confer strong hyper-sensitivity to IR. SMG-1 is a phosphoinositide-3 kinase (PI3K) involved in mediating nonsense-mediated mRNA decay (NMD) of transcripts containing premature stop codons and related to the ATM and ATR kinases which are at the apex of DNA da...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Gonzalez-Huici, V., Wang, B., Gartner, A. Tags: Genome Integrity and Transmission Source Type: research
Genetics of Genome-Wide Recombination Rate Evolution in Mice from an Isolated Island [Genome Integrity and Transmission]
Recombination rate is a heritable quantitative trait that evolves despite the fundamentally conserved role that recombination plays in meiosis. Differences in recombination rate can alter the landscape of the genome and the genetic diversity of populations. Yet our understanding of the genetic basis of recombination rate evolution in nature remains limited. We used wild house mice (Mus musculus domesticus) from Gough Island (GI), which diverged recently from their mainland counterparts, to characterize the genetics of recombination rate evolution. We quantified genome-wide autosomal recombination rates by immunofluorescenc...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Wang, R. J., Payseur, B. A. Tags: Genome Integrity and Transmission Source Type: research
Maternal Haploid, a Metalloprotease Enriched at the Largest Satellite Repeat and Essential for Genome Integrity in Drosophila Embryos [Genome Integrity and Transmission]
The incorporation of the paternal genome into the zygote during fertilization requires chromatin remodeling. The maternal haploid (mh) mutation in Drosophila affects this process and leads to the formation of haploid embryos without the paternal genome. mh encodes the Drosophila homolog of SPRTN, a conserved protease essential for resolving DNA–protein cross-linked products. Here we characterize the role of MH in genome maintenance. It is not understood how MH protects the paternal genome during fertilization, particularly in light of our finding that MH is present in both parental pronuclei during zygote formation. ...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Tang, X., Cao, J., Zhang, L., Huang, Y., Zhang, Q., Rong, Y. S. Tags: Genome Integrity and Transmission Source Type: research
Pharmacological Inhibition of the DNA Damage Checkpoint Prevents Radiation-Induced Oocyte Death [Genome Integrity and Transmission]
Ovarian function is directly correlated with survival of the primordial follicle reserve. Women diagnosed with cancer have a primary imperative of treating the cancer, but since the resting oocytes are hypersensitive to the DNA-damaging modalities of certain chemo- and radiotherapeutic regimens, such patients face the collateral outcome of premature loss of fertility and ovarian endocrine function. Current options for fertility preservation primarily include the collection and cryopreservation of oocytes or in vitro-fertilized oocytes, but this necessitates a delay in cancer treatment and additional assisted reproductive t...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Rinaldi, V. D., Hsieh, K., Munroe, R., Bolcun-Filas, E., Schimenti, J. C. Tags: Genome Integrity and Transmission Source Type: research
A Lysine Desert Protects a Novel Domain in the Slx5-Slx8 SUMO Targeted Ub Ligase To Maintain Sumoylation Levels in Saccharomyces cerevisiae [Genome Integrity and Transmission]
Protein modification by the small ubiquitin-like modifier (SUMO) plays important roles in genome maintenance. In Saccharomyces cerevisiae, proper regulation of sumoylation is known to be essential for viability in certain DNA repair mutants. Here, we find the opposite result; proper regulation of sumoylation is lethal in certain DNA repair mutants. Yeast cells lacking the repair factors TDP1 and WSS1 are synthetically lethal due to their redundant roles in removing Top1-DNA covalent complexes (Top1ccs). A screen for suppressors of tdp1 wss1 synthetic lethality isolated mutations in genes known to control global sumoylation...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Sharma, P., Mullen, J. R., Li, M., Zaratiegui, M., Bunting, S. F., Brill, S. J. Tags: Genome Integrity and Transmission Source Type: research
Genome-Wide Association Analyses Based on Broadly Different Specifications for Prior Distributions, Genomic Windows, and Estimation Methods [Statistical Genetics and Genomics]
A currently popular strategy (EMMAX) for genome-wide association (GWA) analysis infers association for the specific marker of interest by treating its effect as fixed while treating all other marker effects as classical Gaussian random effects. It may be more statistically coherent to specify all markers as sharing the same prior distribution, whether that distribution is Gaussian, heavy-tailed (BayesA), or has variable selection specifications based on a mixture of, say, two Gaussian distributions [stochastic search and variable selection (SSVS)]. Furthermore, all such GWA inference should be formally based on posterior p...
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Chen, C., Steibel, J. P., Tempelman, R. J. Tags: Statistical Genetics and Genomics Source Type: research
