Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “genetic interaction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed2005

The Ras and Rho GTPases genetically interact to co-ordinately regulate cell polarity during development in Penicillium marneffei.

Ras and Rho GTPases have been examined in a wide variety of eukaryotes and play varied and often overlapping roles in cell polarization and development. Studies in Saccharomyces cerevisiae and mammalian cells have defined some of the central activities of these GTPases. However, these paradigms do not explain the role of these proteins in all eukaryotes. Unlike yeast, but like more complex eukaryotes, filamentous fungi have Rac-like proteins in addition to Ras and Cdc42. To investigate the unique functions of these proteins and determine how they interact to co-ordinately regulate morphogenesis during growth and development we undertook a genetic analysis of GTPase function by generating double mutants of the Rho GTPases cflA and cflB and the newly isolated Ras GTPase rasA from the dimorphic pathogenic fungus, Penicillium marneffei. P. marneffei growth at 25 degrees C is as multinucleate, septate, branched hyphae which are capable of undergoing asexual development (conidiation), while at 37 degrees C, uninucleate pathogenic yeast cells which divide by fission are produced. Here we show that RasA (Ras) acts upstream of CflA (Cdc42) to regulate germination of spores and polarized growth of both hyphal and yeast cells, while also exhibiting CflA-independent activities. CflA (Cdc42) and CflB (Rac) co-ordinately control hyphal cell polarization despite also having unique roles in regulating conidial germination and polarized growth of yeast cells (CflA) and polarized growth of conidiophore cell types and hyphal branching (CflB).

Cell Compartmentation↗
PubMed1996

Genetic interactions among vestigial, hairy, and Notch suggest a role of vestigial in the differentiation of epidermal and neural cells of the wing and halter of Drosophila melanogaster.

In this paper we describe the results of genetic analysis of the vestigial locus by studying its interactions with hairy and Notch loci in Drosophila melanogaster. Different vestigial alleles in homo- and heterozygous combination with different hairy alleles show synergism in increasing both cell death and formation of ectopic bristles and produce ectopic veins. Interactions between N and vg also show synergism in increasing cell death and formation of ectopic bristles. Only synergism in cell death is seen between h and N. The interactions indicate that vg product plays a role in the differentiation of epidermal and neural cells of the wing disc by interacting with N and h products either directly or indirectly. Mechanisms of molecular interactions among the three loci are discussed.

Animals↗
PubMed1994

Characterization of the yeast (1-->6)-beta-glucan biosynthetic components, Kre6p and Skn1p, and genetic interactions between the PKC1 pathway and extracellular matrix assembly.

A characterization of the S. cerevisiae KRE6 and SKN1 gene products extends previous genetic studies on their role in (1-->6)-beta-glucan biosynthesis (Roemer, T., and H. Bussey. 1991. Yeast beta-glucan synthesis: KRE6 encodes a predicted type II membrane protein required for glucan synthesis in vivo and for glucan synthase activity in vitro. Proc. Natl. Acad. Sci. USA. 88:11295-11299; Roemer, T., S. Delaney, and H. Bussey. 1993. SKN1 and KRE6 define a pair of functional homologs encoding putative membrane proteins involved in beta-glucan synthesis. Mol. Cell. Biol. 13:4039-4048). KRE6 and SKN1 are predicted to encode homologous proteins that participate in assembly of the cell wall polymer (1-->6)-beta-glucan. KRE6 and SKN1 encode phosphorylated integral-membrane glycoproteins, with Kre6p likely localized within a Golgi subcompartment. Deletion of both these genes is shown to result in a dramatic disorganization of cell wall ultrastructure. Consistent with their direct role in the assembly of this polymer, both Kre6p and Skn1p possess COOH-terminal domains with significant sequence similarity to two recently identified glucan-binding proteins. Deletion of the yeast protein kinase C homolog, PKC1, leads to a lysis defect (Levin, D. E., and E. Bartlett-Heubusch. 1992. Mutants in the S. cerevisiae PKC1 gene display a cell cycle-specific osmotic stability defect. J. Cell Biol. 116:1221-1229). Kre6p when even mildly overproduced, can suppress this pkc1 lysis defect. When mutated, several KRE pathway genes and members of the PKC1-mediated MAP kinase pathway have synthetic lethal interactions as double mutants. These suppression and synthetic lethal interactions, as well as reduced beta-glucan and mannan levels in the pkc1 null wall, support a role for the PKC1 pathway functioning in cell wall assembly. PKC1 potentially participates in cell wall assembly by regulating the synthesis of cell wall components, including (1-->6)-beta-glucan.

Amino Acid Sequence↗
PubMed1999

Genome complexity, robustness and genetic interactions in digital organisms.

Digital organisms are computer programs that self-replicate, mutate and adapt by natural selection. They offer an opportunity to test generalizations about living systems that may extend beyond the organic life that biologists usually study. Here we have generated two classes of digital organism: simple programs selected solely for rapid replication, and complex programs selected to perform mathematical operations that accelerate replication through a set of defined 'metabolic' rewards. To examine the differences in their genetic architecture, we introduced millions of single and multiple mutations into each organism and measured the effects on the organism's fitness. The complex organisms are more robust than the simple ones with respect to the average effects of single mutations. Interactions among mutations are common and usually yield higher fitness than predicted from the component mutations assuming multiplicative effects; such interactions are especially important in the complex organisms. Frequent interactions among mutations have also been seen in bacteria, fungi and fruitflies. Our findings support the view that interactions are a general feature of genetic systems.

Biological Evolution↗
PubMed2006

Genetic interactions of a putative Arabidopsis thaliana ubiquitin-ligase with components of the Saccharomyces cerevisiae ubiquitination machinery.

The feasibility of using the Saccharomyces cerevisiae genetic tools to get insights into the function of a plant-specific ubiquitin-ligase was examined. ATL2 is a potential ubiquitin-ligase of the RING-H2 type that was originally isolated as a conditionally toxic Arabidopsis cDNA when overexpressed in yeast. ATL2 is a member of an Arabidopsis family that comprises 80 proteins. After testing cDNAs from 25 ATL members for toxicity we found that in addition to ATL2 only ATL63 was toxic, suggesting specific interactions of each one of these two ATLs in yeast. We seek to identify suppressors of the ATL2 toxicity in yeast and we found that toxicity was suppressed by knock-out mutations on different components of the ubiquitination pathway. Suppression was achieved in four deubiquitinating enzyme mutants and in one ubiquitin-conjugating enzyme mutant. A model is proposed in which Ubc4 and ATL2 act together to target for degradation one or more essential yeast proteins, Doa4/Ubp4, Ubp6 and Ubp14 have a role in disassembling ubiquitin chains on the target proteins and Ubp15 protects ATL2 from auto-ubiquitination. We presuppose that our approach can be further utilized to analyze the function of this distinctive class of ubiquitin-ligases in yeast as well as in Arabidopsis.

Arabidopsis↗
PubMed1985

Genetic interactions of broad host-range plasmid RK2: evidence for a complex replication regulon.

The kil and kor genes of RK2 are novel genetic determinants further that the kil and kor network constitutes a replication regulon, and that perhaps the function of this regulon is to ensure expression of trfA at appropriate levels. The complexity of this regulon may reflect an ability of the system to adapt to the intracellular environments of a variety of hosts. Indeed, there is tantalizing evidence that regions encoding kil or kor genes are important to host range (1,2,6,28; Schmidhauser and Helinski, pers. comm.). We are therefore hopeful that the study of these genes and the eventual determination of the molecular basis of their actions will lead to a complete understanding of the replication control and broad host range capability of IncP plasmids.

Bacterial Proteins↗
PubMed1955

Evidence for genetic interaction between non-infectious and infectious influenza A viruses.

Influenza virus rendered non-infectious by ultraviolet irradiation retained ability to "exchange" genetic traits with related virus, resulting in recombined forms. Sedimentation studies indicated association of recombinining activity with particles approximately the size of influenza virus. Genetic activity was not demonstrated when virus was more severely disrupted in attempts to observe phenomena analogous to bacterial transformation. Irradiated virus was also shown to remain capable of genetic exchange for at least 4 days after inoculation into embryonate eggs. In contrast infectious virus becomes insusceptible to genetic exchange after 1 hour incubation in eggs. The importance of this delayed recombination phenomenon to processes of virus evolution and influenza strain variation was discussed.

Humans↗
PubMed1994

Genetic interactions among genes involved in the STT4-PKC1 pathway of Saccharomyces cerevisiae.

Loss of yeast protein kinase C function results in three distinct phenotypes: staurosporine sensitivity, cell lysis and blockage of cell cycle progression at the G2/M boundary. Genetic analysis of the PKC1/STT1 protein kinase C gene and its interactions with STT4, encoding an upstream phosphatidylinositol 4-kinase, and BCK1, encoding a downstream protein kinase, reveal that they form part of a single pathway. However, the BCK1-20 mutation (a gain-of-function mutation of BCK1) or overexpression of PKC1 cannot suppress all of the phenotypes caused by the loss of STT4 function, strongly suggesting the existence of a branch point between STT4 and PKC1. We also describe the MSS4 gene, a multicopy suppressor of the temperature-sensitive stt4-1 mutation. MSS4 is predicted to encode a hydrophilic protein of 779 amino acid residues and is essential for cell growth. Based on genetic and biochemical data, we suggest that MSS4 acts downstream of STT4, but in a pathway that does not involve PKC1.

1-Phosphatidylinositol 4-Kinase↗
PubMed1998

Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning.

In the developing vertebrate hindbrain Hoxa1 and Hoxb1 play important roles in patterning segmental units (rhombomeres). In this study, genetic analysis of double mutants demonstrates that both Hoxa1 and Hoxb1 participate in the establishment and maintenance of Hoxb1 expression in rhombomere 4 through auto- and para-regulatory interactions. The generation of a targeted mutation in a Hoxb1 3' retinoic acid response element (RARE) shows that it is required for establishing early high levels of Hoxb1 expression in neural ectoderm. Double mutant analysis with this Hoxb1(3'RARE) allele and other targeted loss-of-function alleles from both Hoxa1 and Hoxb1 reveals synergy between these genes. In the absence of both genes, a territory appears in the region of r4, but the earliest r4 marker, the Eph tyrosine kinase receptor EphA2, fails to be activated. This suggests a failure to initiate rather than maintain the specification of r4 identity and defines new roles for both Hoxb1 and Hoxa1 in early patterning events in r4. Our genetic analysis shows that individual members of the vertebrate labial-related genes have multiple roles in different steps governing segmental processes in the developing hindbrain.

Animals↗
PubMed1998

Genetic interactions between mutants of the 'error-prone' repair group of Saccharomyces cerevisiae and their effect on recombination and mutagenesis.

We have created an isogenic series of yeast strains that carry genetic systems to monitor different types of recombination and mutation [B. Liefshitz, A. Parket, R. Maya, M. Kupiec, The role of DNA repair genes in recombination between repeated sequences in yeast, Genetics 140 (1995) 1199-1211.]. In the present study we characterize the effect of mutations in genes of the 'error-prone' or postreplicative repair group on recombination and mutation. We show that rad5 and rad18 strains have elevated levels of spontaneous recombination, both of ectopic gene conversion and of recombination between direct repeats. The increase in recombination levels is similar in both mutants and in the rad5 rad18 double mutant, suggesting that the RAD5 and RAD18 gene products act together with respect to spontaneous recombination. In contrast, RAD5 and RAD18 play alternative roles in mutagenic repair: mutations in each of these genes elevate spontaneous forward mutation at the CAN1 locus, but when both genes are deleted, a low level of spontaneous mutagenesis is seen. The RAD5/RAD18 pathway of mutagenic repair is dependent on the REV3-encoded translesion polymerase. We analyze the interactions between the RAD5 and RAD18 gene products and other repair genes. The high recombination levels seen in rad5 and rad18 mutants is dependent on the RAD1, RAD51, RAD52, and RAD57 genes. The Srs2 helicase plays an important role in creating the recombinogenic substrate(s) processed by the RAD5 and RAD18 gene products.

Adenosine Triphosphatases↗
PubMed2000

Surfactant proteins A and B as interactive genetic determinants of neonatal respiratory distress syndrome.

Prematurity is the most important risk factor predisposing to neonatal respiratory distress syndrome (RDS). Genetic factors are likely to contribute to the risk of this complex disease. The present study was designed to investigate whether the surfactant protein B (SP-B) gene or interaction between the SP-A and SP-B genes has a role in the genetic susceptibility to RDS. The genotype analyses were performed on 684 prematurely born neonates, of whom 184 developed RDS. Of the two SP-B polymorphisms genotyped, the Ile131Thr variation affects a putative N-terminal N:-linked glycosylation site of proSP-B and the length variation of intron 4 has previously been suggested to associate with RDS. Neither of the two SP-B polymorphisms associated directly with RDS or with prematurity. Instead, our data show that the previously identified association between SP-A alleles and RDS was dependent on the SP-B Ile131Thr genotype. On the basis of chi(2) and logistic regression analyses, the SP-A allele, haplotype and genotype distributions differed significantly between the RDS infants and controls only when the SP-B genotype was Thr/Thr. Among the infants born before 32 weeks of gestation and having the SP-B genotype Thr/Thr, the SP-A1 allele 6A(2) was over-represented in RDS group compared with controls (P = 0.001, OR = 4.7, CI 1.8-12.2). In the same comparison, the SP-A1 allele 6A(3) was under-represented in RDS (P = 0.001, OR = 0.2, CI 0.1-0.6). We propose that the SP-B Ile131Thr polymorphism is a determinant for certain SP-A alleles as factors causing genetic susceptibility to RDS (6A(2), 1A(0)) or protection against it (6A(3), 1A(2)).

Alleles↗
PubMed1994

Genetic interactions between the yeast RNA helicase homolog Prp16 and spliceosomal snRNAs identify candidate ligands for the Prp16 RNA-dependent ATPase.

Pre-mRNA splicing occurs in a large and dynamic ribonucleoprotein complex, the spliceosome. Several protein factors involved in splicing are homologous to a family of RNA-dependent ATPases, the so-called DEAD/DEAH proteins. A subset of these factors exhibit RNA helicase activity in vitro. The DEAD/DEAH proteins involved in splicing are thought to mediate RNA conformational rearrangements during spliceosome assembly. However, the RNA ligands for these factors are currently unknown. Here, we present genetic evidence in Saccharomyces cerevisiae for a functional interaction between the DEAH protein Prp16, and the U6 and U2 spliceosomal snRNAs. Using a library of mutagenized U6 snRNA genes, we have identified 14 strong suppressors of the cold-sensitive (cs) allele, prp16-302. Remarkably, each suppressor contains a single nucleotide deletion of 1 of the 6 residues that lie immediately upstream of a sequence in U6 that interacts with the 5' splice site. Analysis of site-directed mutations revealed that nucleotide substitutions in the adjacent U2-U6 helix I structure also suppress prp16-302, albeit more weakly. The U6 suppressors tested also partially reverse the phenotype of two other cs alleles, prp16-1 and prp16-301, but not the four temperature-sensitive alleles tested. Finally, overexpression of each cs allele exacerbates its recessive growth phenotype and confers a dominant negative cs phenotype. We propose that the snRNA suppressors function by destabilizing an interaction between the U2-U6 complex and a hypothetical factor (X), which is trapped by cs mutants of PRP16. The phenotypes of overexpressed prp16 alleles are consistent with the model that this trapped interaction inhibits the dissociation of Prp16 from the spliceosome. We discuss the intriguing possibility that factor X is Prp16 itself.

Adenosine Triphosphatases↗