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Plos Genetics : the Yeast Rab Gtpase Ypt1 Modulates Unfolded Prote...

By: Sabarinath Jayaseelan

Description : The unfolded protein response (UPR) is a conserved mechanism that mitigates accumulation of unfolded proteins in the ER. The yeast UPR is subject to intricate post-transcriptional regulation, involving recruitment of the RNA encoding the Hac1 transcription factor to the ER and its unconventional splicing. To investigate the mechanisms underlying regulation of the UPR, we screened the yeast proteome for proteins that specifically interact with HAC1 RNA. Prot...

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Plos Genetics : Hectd2is Associated with Susceptibility to Mouse a...

By: George A. Carlson

Description : Prion diseases are fatal transmissible neurodegenerative disorders, which include Scrapie, Bovine Spongiform Encephalopathy (BSE), Creutzfeldt-Jakob Disease (CJD), and kuru. They are characterised by a prolonged clinically silent incubation period, variation in which is determined by many factors, including genetic background. We have used a heterogeneous stock of mice to identify Hectd2, an E3 ubiquitin ligase, as a quantitative trait gene for prion diseas...

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Plos Genetics : a Fundamental Regulatory Mechanism Operating Throu...

By: Josep Casadesús

Description : DNA topology has fundamental control over the ability of transcription factors to access their target DNA sites at gene promoters. However, the influence of DNA topology on protein–DNA and protein–protein interactions is poorly understood. For example, relaxation of DNA supercoiling strongly induces the well-studied pathogenicity gene ssrA (also called spiR) in Salmonella enterica, but neither the mechanism nor the proteins involved are known. We have found...

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Plos Genetics : Clathrin and Ap2 Are Required for Phagocytic Recep...

By: Anton Gartner

Description : Clathrin and the multi-subunit adaptor protein complex AP2 are central players in clathrin-mediated endocytosis by which the cell selectively internalizes surface materials. Here, we report the essential role of clathrin and AP2 in phagocytosis of apoptotic cells. In Caenorhabditis elegans, depletion of the clathrin heavy chain CHC-1 and individual components of AP2 led to a significant accumulation of germ cell corpses, which resulted from defects in both ...

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Plos Genetics : Allele-specific Krt1 Expression is a Complex Trait...

By: Andrew Clark

Description : The differential expression of alleles occurs commonly in humans and is likely an important genetic factor underlying heritable differences in phenotypic traits. Understanding the molecular basis of allelic expression differences is thus an important challenge. Although many genes have been shown to display differential allelic expression, this is the first study to examine in detail the cumulative effects of multiple cis-regulatory polymorphisms responsibl...

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Plos Genetics : Meiotic Chromosome Synapsis-promoting Proteins Ant...

By: James E. Haber

Description : Sgs1, the budding yeast homolog of the mammalian BLM helicase, has been implicated in preventing excess recombination during both vegetative growth and meiosis. Most meiotic crossover (CO) recombination requires full function of a set of yeast proteins (Zip1, Zip2, Zip3, Zip4/Spo22, Mer3, Msh4, and Msh5, termed the SIC or ZMM proteins) that are also required for homologous chromosome synapsis. We report here genetic and molecular assays showing that sgs1 si...

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Plos Genetics : Identification and Replication of Three Novel Myop...

By: Greg Gibson

Description : Refractive error is a highly heritable quantitative trait responsible for considerable morbidity. Following an initial genomewide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted fine-scale association mapping using high-resolution linkage disequilibrium unit (LDU) maps. We used a preliminary discovery marker set across the 30-Mb region with an average SNP density of 1 SNP/15 kb (Map 1). Map...

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Plos Genetics : Sox6 Directly Silences Epsilon Globin Expression i...

By: Gregory Barsh

Description : Sox6 is a member of the Sox transcription factor family that is defined by the conserved high mobility group (HMG) DNA binding domain, first described in the testis determining gene, Sry. Previous studies have suggested that Sox6 plays a role in the development of the central nervous system, cartilage, and muscle. In the Sox6-deficient mouse, p100H, ey globin is persistently expressed, and increased numbers of nucleated red cells are present in the fetal ci...

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Plos Genetics : Interallelic and Intergenic Incompatibilities of t...

By: Michael W. Nachman

Description : The Dobzhansky-Muller model of incompatibilities explains reproductive isolation between species by incorrect epistatic interactions. Although the mechanisms of speciation are of great interest, no incompatibility has been characterized at the gene level in mammals. The Hybrid sterility 1 gene (Hst1) participates in the arrest of meiosis in F1 males of certain strains from two Mus musculus subspecies, e.g., PWD from M. m. musculus and C57BL/6J (henceforth B...

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Plos Genetics : Meta-analysis of Genome-wide Scans for Human Adult...

By: Peter M. Visscher

Description : Recent genome-wide (GW) scans have identified several independent loci affecting human stature, but their contribution through the different skeletal components of height is still poorly understood. We carried out a genome-wide scan in 12,611 participants, followed by replication in an additional 7,187 individuals, and identified 17 genomic regions with GWsignificant association with height. Of these, two are entirely novel (rs11809207 in CATSPER4, combined...

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Plos Genetics : Diverse Forms of Rps9 Splicing Are Part of an Evol...

By: Leonid Kruglyak

Description : Ribosomal proteins are essential to life. While the functions of ribosomal protein-encoding genes (RPGs) are highly conserved, the evolution of their regulatory mechanisms is remarkably dynamic. In Saccharomyces cerevisiae, RPGs are unusual in that they are commonly present as two highly similar gene copies and in that they are over-represented among intron-containing genes. To investigate the role of introns in the regulation of RPG expression, we construc...

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Plos Genetics : Scavenger Receptors Mediate the Role of Sumo and F...

By: Eric Rulifson

Description : SUMOylation participates in ecdysteroid biosynthesis at the onset of metamorphosis in Drosophila melanogaster. Silencing the Drosophila SUMO homologue smt3 in the prothoracic gland leads to reduced lipid content, low ecdysone titers, and a block in the larval–pupal transition. Here we show that the SR-BI family of Scavenger Receptors mediates SUMO functions. Reduced levels of Snmp1 compromise lipid uptake in the prothoracic gland. In addition, overexpressio...

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Plos Genetics : Assessing Systems Properties of Yeast Mitochondria...

By: Stuart K. Kim

Description : Mitochondria carry out specialized functions: compartmentalized, yet integrated into the metabolic and signaling processes of the cell. Although many mitochondrial proteins have been identified, understanding their functional interrelationships has been a challenge. Here we construct a comprehensive network of the mitochondrial system. We integrated genome-wide datasets to generate an accurate and inclusive mitochondrial parts list. Together with benchmarke...

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Plos Genetics : Azospirillum Genomes Reveal Transition of Bacteria...

By: Paul M. Richardson

Description : Fossil records indicate that life appeared in marine environments ,3.5 billion years ago (Gyr) and transitioned to terrestrial ecosystems nearly 2.5 Gyr. Sequence analysis suggests that ‘‘hydrobacteria’’ and ‘‘terrabacteria’’ might have diverged as early as 3 Gyr. Bacteria of the genus Azospirillum are associated with roots of terrestrial plants: however, virtually all their close relatives are aquatic. We obtained genome sequences of two Azospirillum speci...

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Plos Genetics : Polycomb Repressive Complex 2 Controls the Embryo-...

By: Gregory P. Copenhaver

Description : Polycomb repressive complex 2 (PRC2) is a key regulator of epigenetic states catalyzing histone H3 lysine 27 trimethylation (H3K27me3), a repressive chromatin mark. PRC2 composition is conserved from humans to plants, but the function of PRC2 during the early stage of plant life is unclear beyond the fact that it is required for the development of endosperm, a nutritive tissue that supports embryo growth. Circumventing the requirement of PRC2 in endosperm a...

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Plos Genetics : the Sumo Isopeptidase Ulp2P is Required to Prevent...

By: Orna Cohen-fix

Description : SUMO conjugation is a key regulator of the cellular response to DNA replication stress, acting in part to control recombination at stalled DNA replication forks. Here we examine recombination-related phenotypes in yeast mutants defective for the SUMO de-conjugating/chain-editing enzyme Ulp2p. We find that spontaneous recombination is elevated in ulp2 strains and that recombination DNA repair is essential for ulp2 survival. In contrast to other SUMO pathway ...

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Plos Genetics : Mice with Alopecia, Osteoporosis, and Systemic Amy...

By: Marcy E. MacDonald

Description : Protein palmitoylation has emerged as an important mechanism for regulating protein trafficking, stability, and protein– protein interactions: however, its relevance to disease processes is not clear. Using a genome-wide, phenotype driven Nethyl- N-nitrosourea–mediated mutagenesis screen, we identified mice with failure to thrive, shortened life span, skin and hair abnormalities including alopecia, severe osteoporosis, and systemic amyloidosis (both AA and ...

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Plos Genetics : Congenital Heart Disease–causing Gata4 Mutation Di...

By: Scott Baldwin

Description : Defects of atrial and ventricular septation are the most frequent formof congenital heart disease, accounting for almost 50% of all cases. We previously reported that a heterozygous G296S missense mutation of GATA4 caused atrial and ventricular septal defects and pulmonary valve stenosis in humans. GATA4 encodes a cardiac transcription factor, and when deleted in mice it results in cardiac bifida and lethality by embryonic day (E)9.5. In vitro, the mutant G...

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Plos Genetics : the Cpeb Protein Orb2 Has Multiple Functions Durin...

By: Norbert Perrimon

Description : Cytoplasmic Polyadenylation Element Binding (CPEB) proteins are translational regulators that can either activate or repress translation depending on the target mRNA and the specific biological context. There are two CPEB subfamilies and most animals have one or more genes from each. Drosophila has a single CPEB gene, orb and orb2, from each subfamily. orb expression is only detected at high levels in the germline and has critical functions in oogenesis but...

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Plos Genetics : Competitive Repair by Naturally Dispersed Repetiti...

By: Gregory P. Copenhaver

Description : Genome rearrangements often result from non-allelic homologous recombination (NAHR) between repetitive DNA elements dispersed throughout the genome. Here we systematically analyze NAHR between Ty retrotransposons using a genome-wide approach that exploits unique features of Saccharomyces cerevisiae purebred and Saccharomyces cerevisiae/ Saccharomyces bayanus hybrid diploids. We find that DNA double-strand breaks (DSBs) induce NAHR–dependent rearrangements u...

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