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At least 343 records · Page 19Linked to original sources
PubMed2006

A single-strand conformation polymorphism (SSCP) approach for investigating genetic interactions of Schistosoma haematobium and Schistosoma guineensis in Loum, Cameroon.

Single-strand conformation polymorphism (SSCP) analysis of the second internal transcribed spacer (ITS2) of nuclear ribosomal DNA provides a molecular tool for the identification of Schistosoma haematobium, Schistosoma guineensis and the hybrids of these two species. This molecular tool was utilized to provide a detailed analysis of the interactions between S. haematobium and S. guineensis in hybrid zones of Loum, Littoral Province, Cameroon. Individual hybrid schistosomes were identified within the natural populations collected from Loum in 1990, 1999 and 2000, which would have been misidentified as S. haematobium using solely morphological and sequence criteria. This study indicates the complexities of the hybridization between S. haematobium and S. guineensis and emphasizes the importance of assessing morphological, biological and molecular data to gain insights into the interaction of these two species over time.

Animals↗
PubMed1996

Genetic interaction of DED1 encoding a putative ATP-dependent RNA helicase with SRM1 encoding a mammalian RCC1 homolog in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae temperature-sensitive mutants srm1-1, mtr1-2 and prp20-1 carry alleles of a gene encoding a homolog of mammalian RCC1. In order to identify a protein interacting with RCC1, a series of suppressors of the srm1-1 mutation were isolated as cold-sensitive mutants and one of the mutants, designated ded1-21, was found to be defective in the DED1 gene. The double mutant, srm1-1 ded1-21, could grow at 35 degrees C, but not at 37 degrees C. A revertant of srm1-1 ded1-21 that became able to grow at 37 degrees C acquired another mutation in the SRM1 gene, indicating the tight relationship between SRM1 and DED1. In all the rcc1- strains examined, the amount of mutated SRM1 proteins was reduced or not detectable at the nonpermissive temperature. While mutated SRM1 protein was stabilized in all of the rcc1- strains by the ded1-21 mutation, the ded1-21 mutation suppressed both srm1-1 and mtr1-2, but not the prp20-1 mutation, contrary to the previous finding that overproduction of the S. cerevisiae Ran homolog GSP1 suppresses prp20-1, but not srm1-1 or mtr1-2.

Cell Cycle Proteins↗
PubMed1999

Genetic interactions between a null allele of the RIT1 gene encoding an initiator tRNA-specific modification enzyme and genes encoding translation factors in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae gene RIT1 encodes a phospho-ribosyl transferase that exclusively modifies the initiator tRNA (tRNAMet(i)) by the addition of a 2'-O-ribosyl phosphate group to Adenosine 64. As a result, tRNAMet(i) is prevented from participating in the elongation steps of protein synthesis. We previously showed that the modification is not essential for the function of tRNAMet(i) in the initiation of translation, since rit1 null strains are viable and show no obvious growth defects. Here, we demonstrate that yeast strains in which a rit1 null allele is combined with mutations in any of the genes for the three subunits of eukaryotic initiation factor-2 (eIF-2), or with disruption alleles of two of the four initiator methionine tRNA (IMT) genes, show synergistic growth defects. A multicopy plasmid carrying an IMT gene can alleviate these defects. On the other hand, introduction of a high-copy-number plasmid carrying the TEF2 gene, which encodes the eukaryotic elongation factor 1alpha (eEF-1alpha), into rit1 null strains with two intact IMT genes had the opposite effect, indicating that increased levels of eEF-1alpha are deleterious to these strains, presumably due to sequestration of the unmodified met-tRNAMet(i) for elongation. Thus, under conditions in which the components of the ternary met-tRNAMet(i):GTP:eIF-2 complex become limiting or are functionally impaired, the presence of the 2'-O-ribosyl phosphate modification in tRNAMet(i) is important for the provision of adequate amounts of tRNAMet(i) for formation of this ternary complex.

Alleles↗
PubMed2001

Sna41goa1, a novel mutation causing G1/S arrest in fission yeast, is defective in a CDC45 homolog and interacts genetically with polalpha.

Proteins involved in the initiation of DNA replication play critical roles in the assembly and loading of replication complexes at replication origins. To gain further insight into the regulation of initiation, we screened in fission yeast for temperature-sensitive mutants which arrested at the G1/S boundary, and isolated nine mutants which arrested with a 1C DNA content at 36 degrees C. By linkage analysis, two complementation groups were identified which were not allelic to known G1 arrest mutations. One of the mutants isolated, sna41goul, arrested with a G1 DNA content and expressed a pleiomorphic phenotype, i.e., a mixture of cut and cdc phenotypes, at 36 degrees C. The point of arrest was identified as after START but before the hydroxyurea-induced block, by taking advantage of the mutant rad26.a14, which has a defect in an early S phase-specific checkpoint, and by performing reciprocal shift experiments. sna41 goal is allelic to sna41+, which is homologous to the CDC45 gene of budding yeast, and the mutation lies in a motif that is highly conserved in Cdc45-related proteins. The temperature sensitivity of the sna41goal mutant can be suppressed to some extent by ts mutations in polalpha. Our genetic results are consistent with a model in which Cdc45 plays crucial roles in the assembly of the replication apparatus at replication origins.

Carrier Proteins↗
PubMed1995

Possible relevance of phospholipid abnormalities and genetic interactions in psychiatric disorders: the relationship between dyslexia and schizophrenia.

The fatty acids of cell membrane phospholipids are essential for normal membrane structures, for the functioning of membrane-bound and membrane-associated proteins and for normal cell-signalling responses. In dyslexia, there is evidence for reduced incorporation of docosahexaenoic acid and arachidonic acid into cell membranes, while in schizophrenia, there is evidence for an increased rate of docosahexaenoic acid and arachidonic acid loss from membranes because of enhanced phospholipase A2 activity. The presence of both defects will cause a much greater degree of abnormality than either one alone. It is hypothesized that unequivocal clinical schizophrenia may occur when both genes are present in the same individual. The dyslexia gene along will produce dyslexia while the schizophrenia gene alone may produce bipolar or schizoaffective disorders. These proposals could explain: 1. The reduced asymmetry of the brain, especially of the planum temporale in both schizophrenia and dyslexia; 2. The schizotypal personality characteristics of dyslexics; 3. The increased risks of dyslexia in families with a schizophrenic proband; 4. The increased risks of bipolar and schizoaffective disorders in families with a schizophrenic proband; 5. The earlier onset and possibly increased severity of both disorders in males since females have a lower requirement for arachidonic acid and docosahexaenoic acid; 6. The absence of selective pressure against schizophrenia since reproduction would be impaired only when the schizophrenic gene coexisted with a dyslexic gene. The schizophrenic gene alone might even lead to improved reproductive performance.

Arachidonic Acid↗
PubMed2005

Function and regulation of Alx4 in limb development: complex genetic interactions with Gli3 and Shh.

The role of the aristaless-related homeobox gene Alx4 in antero-posterior (AP-) patterning of the developing vertebrate limb has remained somewhat elusive. Polydactyly of Alx4 mutant mice is known to be accompanied by ectopic anterior expression of genes like Shh, Fgf4 and 5'Hoxd. We reported previously that polydactyly in Alx4 mutant mice requires SHH signaling, but we now show that in early Alx4-/- limb buds the anterior ectopic expression of Fgf4 and Hoxd13, and therefore disruption of AP-patterning, occurs independently of SHH signaling. To better understand how Alx4 functions in the pathways that regulate AP-patterning, we also studied genomic regulatory sequences that are capable of directing expression of a reporter gene in a pattern corresponding to endogenous Alx4 expression in anterior limb bud mesenchyme. We observed, as expected for authentic Alx4 expression, expansion of reporter construct expression in a Shh-/- background. Total lack of reporter expression in a Gli3-/- background confirms the existence of Gli3-dependent and -independent Alx4 expression in the limb bud. Apparently, these two modules of Alx4 expression are linked to dissimilar functions.

Animals↗
PubMed2003

Genetic interactions among ZDS1,2, CDC37, and protein kinase CK2 in Saccharomyces cerevisiae.

We report here the identification of the homologous gene pair ZDS1,2 as multicopy suppressors of a temperature-sensitive allele (cka2-13(ts)) of the CKA2 gene encoding the alpha' catalytic subunit of protein kinase CK2. Overexpression of ZDS1,2 suppressed the temperature sensitivity, geldanamycin (GA) sensitivity, slow growth, and flocculation of multiple cka2 alleles and enhanced CK2 activity in vivo toward a known physiological substrate, Fpr3. Consistent with the existence of a recently described positive feedback loop between CK2 and Cdc37, overexpression of ZDS1,2 also suppressed the temperature sensitivity, abnormal morphology, and GA sensitivity of a CK2 phosphorylation-deficient mutant of CDC37, cdc37-S14A, as well as the GA sensitivity of a cdc37-1 allele. A likely basis for all of these effects is our observation that ZDS1,2 overexpression enhances Cdc37 protein levels. Activation of the positive feedback loop between CK2 and Cdc37 likely contributes to the pleiotropic nature of ZDS1,2, as both CK2 and Cdc37 regulate diverse cellular functions.

Adaptor Proteins, Signal Transducing↗
PubMed2000

A genetic interaction between a ubiquitin-like protein and ubiquitin-mediated proteolysis in Dictyostelium discoideum(1).

A ubiquitination factor, NosA, is essential for cellular differentiation in Dictyostelium discoideum. In the absence of nosA, development is blocked, resulting in a developmental arrest at the tight-aggregate stage, when cells differentiate into two precursor cell types, prespore and prestalk cells. Development is restored when a second gene, encoding the ubiquitin-like protein SonA, is inactivated in nosA-mutant cells. SonA has homology over its entire length to Dsk2 from Saccharomyces cerevisiae, a ubiquitin-like protein that is involved in the assembly of the spindle pole body. Dsk2 and SonA are both stable proteins that do not seem to be subjected to degradation via the ubiquitin pathway. SonA does not become ubiquitinated and the intracellular levels of SonA are not affected by the absence of NosA. The high degree of suppression suggests that SonA rescues most or all of the defects caused by the absence of nosA. We propose that NosA and SonA act in concert to control the activity of a developmental regulator that must be deactivated for cells to cross a developmental boundary.

Amino Acid Sequence↗
PubMed2000

Characterization of genetic interactions with RFA1: the role of RPA in DNA replication and telomere maintenance.

Replication protein A (RPA) is a heterotrimeric single-stranded DNA binding protein whose role in DNA replication, recombination and repair has been mainly elucidated through in vitro biochemical studies utilizing the mammalian complex. However, the identification of homologs of all three subunits in Saccharomyces cerevisiae offers the opportunity of examining the in vivo role of RPA. In our laboratory, we have previously isolated a missense allele of the RFA1 gene, encoding the p70 subunit of the RPA complex. Strains containing this mutant allele, rfa1-D228Y, display increased levels of direct-repeat recombination, decreased levels of heteroallelic recombination, UV sensitivity and a S-phase delay. In this study, we have characterized further the role of RPA by screening other replication and repair mutants for a synthetic lethal phenotype in combination with the rfa1-D228Y allele. Among the replication mutants examined, only one displayed a synthetic lethal phenotype, pol12-100, a conditional allele of the B subunit of pol alpha-primase. In addition, a delayed senescence phenotype was observed in raf1-D228Y strains containing a null mutation of HDF1, the S. cerevisiae homolog of the 70 kDa subunit of Ku. Interestingly, a synergistic reduction in telomere length observed in the double mutants suggests that the shortening of telomeres may be the cause of the decreased viability in these strains. Furthermore, this result represents the first evidence of a role for RPA in telomere maintenance.

DNA Polymerase I↗
PubMed2001

Genetic interaction between shibire and comatose mutations in Drosophila suggest a role for snap-receptor complex assembly and disassembly for maintenance of synaptic vesicle cycling.

NSF is an ATPase required for the fusion of secretory vesicles with plasma membrane. Conditional comatose (Drosophila homolog of N-ethylmaleimide sensitive fusion factor (NSF)) mutations in Drosophila block synaptic transmission at restrictive temperature. Current models hold that NSF-mediated dissociation of SNARE (SNAp REceptor) complexes on mature synaptic vesicles primes them for exocytic release. Paralysis in comt mutants thus reflects defective exocytosis due to buildup of unresolved SNARE complexes. Here, we analyze effects of blocking synaptic vesicle recycling on behavioral, physiological and biochemical phenotypes of comt. Behavioral recovery of comt animals and recovery of comt synapses, as assayed by electroretinograms, after exposure to high temperature is faster if synaptic vesicle recycling is simultaneously blocked using shi(ts) mutants. Concurrently, 7S complex buildup in comt shi double mutants is substantially lower than in comt mutants alone. In addition, we find that 7S complexes can form on presynaptic plasma membrane if NSF is inhibited after synaptic-vesicle depletion. Thus, our experiments demonstrate a need for continuous NSF activity required not only for dissociating cis-SNARE complexes on plasma membrane after exocytosis, but also for maintaining these cis-SNARE complexes in a dissociated state.

Animals↗
PubMed2000

Dosage-sensitive, reciprocal genetic interactions between the Abl tyrosine kinase and the putative GEF trio reveal trio's role in axon pathfinding.

The Abelson tyrosine kinase (Abl) is integrated into signal transduction networks regulating axon outgrowth. We have identified the Drosophila trio gene through a mutation that exacerbates the Abl mutant phenotype. Drosophila Trio is an ortholog of mammalian Trio, a protein that contains multiple spectrin-like repeats and two Dbl homology (DH) domains that affect actin cytoskeletal dynamics via the small GTPases Rho and Rac. Phenotypic analysis demonstrates that trio and Abl cooperate in regulating axon outgrowth in the embryonic central nervous system (CNS). Dosage-sensitive interactions between trio and Abl, failed axon connections (fax), and enabled (ena) indicate that Trio is integrated into common signaling networks with these gene products. These observations suggest a mechanism by which Abl-mediated signaling networks influence the actin cytoskeleton in neuronal growth cones.

Animals↗
PubMed2003

Small fitness effects and weak genetic interactions between deleterious mutations in heterozygous loci of the yeast Saccharomyces cerevisiae.

Rare, random mutations were induced in budding yeast by ethyl methanesulfonate (EMS). Clones known to bear a single non-neutral mutation were used to obtain mutant heterozygotes and mutant homozygotes that were later compared with wild-type homozygotes. The average homozygous effect of mutation was an approximately 2% decrease in the growth rate. In heterozygotes, the harmful effect of these relatively mild mutations was reduced approximately fivefold. In a test of epistasis, two heterozygous mutant loci were paired at random. Fitness of the double mutants was best explained by multiplicative action of effects at single loci, with little evidence for epistasis and essentially excluding synergism. In other experiments, the same mutations in haploid and heterozygous diploid clones were compared. Regardless of the haploid phenotypes, mildly deleterious or lethal, fitness of the heterozygotes was decreased by less than half a per cent on average. In general, the results presented here suggest that most mutations tend to exhibit small and weakly interacting effects in heterozygous loci regardless of how harmful they are in haploids or homozygotes.

Clone Cells↗
PubMed2003

Linkage: from particulate to interactive genetics.

Genetics was established on a strict particulate conception of heredity. Genetic linkage, the deviation from independent segregation of Mendelian factors, was conceived as a function of the material allocation of the factors to the chromosomes, rather than to the multiple effects (pleiotropy) of discrete factors. Although linkage maps were abstractions they provided strong support for the chromosomal theory of inheritance. Direct Cytogenetic evidence was scarce until X-ray induced major chromosomal rearrangements allowed direct correlation of genetic and cytological rearrangements. Only with the discovery of the polytenic giant chromosomes in Drosophila larvae in the 1930s were the virtual maps backed up by physical maps of the genetic loci. Genetic linkage became a pivotal experimental tool for the examination of the integration of genetic functions in development and in evolution. Genetic mapping has remained a hallmark of genetic analysis. The location of genes in DNA is a modern extension of the notion of genetic linkage.

Genetics↗