Genome structure of radicicol-induced aneuploids in yeast by array CGH
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE34086 | GEO | 2011/12/31
SECONDARY ACCESSION(S): PRJNA156503
REPOSITORIES: GEO
Similar Datasets
Project description:Aneuploidy, a state of having uneven numbers of chromosomes, is a form of large-effect mutation able to confer adaptive phenotypes under diverse stress conditions. Here we investigate whether pleiotropic stresses could in turn induce aneuploidy in budding yeast. Radicicol was shown to induce high level missegregation of an artificial chromosome (CF). This experiment examines possible aneuploidy of other (“natural”) chromosomes induced by radicicol. Red colonies (lost CF) were first screened by FACS. Possible aneuploids were then subjected to hybridization, with WT as the control.
2011-12-31 | E-GEOD-34086 | biostudies-arrayexpress
Project description:Aneuploidy, a state of having uneven numbers of chromosomes, is a form of large-effect mutation able to confer adaptive phenotypes under diverse stress conditions. Here we investigate whether pleiotropic stresses could in turn induce aneuploidy in budding yeast. Cells exposed to radicicol, an Hsp90 inhibitor, exhibit chromosomal instability. To assess the karyotype of cells with an acquired resistance to radicicol, array CGH was used to compare three stably resistant yeast colonies to a WT strain.
2011-12-31 | GSE34085 | GEO
Project description:Aneuploidy, a state of having uneven numbers of chromosomes, is a form of large-effect mutation able to confer adaptive phenotypes under diverse stress conditions. Here we investigate whether pleiotropic stresses could in turn induce aneuploidy in budding yeast. Cells exposed to radicicol, an Hsp90 inhibitor, exhibit chromosomal instability. To assess the karyotype of cells with an acquired resistance to radicicol, array CGH was used to compare three stably resistant yeast colonies to a WT strain. Single replicates of DNA prepared from radicicol-resistant yeast colonies are compared to a control WT colony.
2011-12-31 | E-GEOD-34085 | biostudies-arrayexpress
Project description:Aneuploidy, an uneven number of chromosomes, leads to severe developmental defects in mammals and is also a hallmark of cancer. However, whether aneuploidy is a driving cause or a consequence of tumor formation remains controversial. Paradoxically, existing studies based on aneuploid yeast and mouse fibroblasts have shown that aneuploidy is usually detrimental to cellular fitness. Here, we examined the effects of aneuploidy on mouse embryonic stem cells. Using a novel genetic scheme, we generated a series of aneuploid cell lines that each carries an extra copy of single chromosomes and then characterized the traits shared by these cell lines. All the aneuploid cell lines had rapid proliferation rates and enhanced colony formation efficiencies. They were less dependent on growth factors for self-renewal and showed a reduced capacity to differentiate in vitro. Moreover, xenografted aneuploid stem cells formed teratomas more efficiently, with features of neoplastic progression. These findings demonstrate that aneuploidy enhances the self-renewal capacities of stem cells and reduces their differentiation abilities.
2017-02-09 | GSE55500 | GEO
Project description:Aneuploidy, the presence of chromosome gains or losses, is a hallmark of cancer and congenital syndromes. Here, we describe KaryoCreate (Karyotype CRISPR Engineered Aneuploidy Technology), a system that enables generation of chromosome-specific aneuploidies by co-expression of a sgRNA targeting chromosome-specific CENPA-binding ɑ-satellite repeats together with dCas9 fused to a mutant form of KNL1. We designed unique and highly specific sgRNAs for 19 out of 24 chromosomes. Expression of these sgRNAs with KNL1Mut-dCas9 leads to missegregation and induction of gains or losses of the targeted chromosome in cellular progeny with an average efficiency of 8% and 12% for gains and losses, respectively (up to 20%), tested and validated across 9 chromosomes. Using KaryoCreate in colon epithelial cells, we show that chromosome 18q loss, a frequent occurrence in gastrointestinal cancers, promotes resistance to TGFβ, likely due to synergistic hemizygous deletion of multiple genes. Altogether, we describe a novel technology to create and study chromosome missegregation and aneuploidy in the context of cancer and beyond.
2023-08-14 | GSE217325 | GEO
Project description:Aneuploidy, the presence of chromosome gains or losses, is a hallmark of cancer and congenital syndromes. Here, we describe KaryoCreate (Karyotype CRISPR Engineered Aneuploidy Technology), a system that enables generation of chromosome-specific aneuploidies by co-expression of a sgRNA targeting chromosome-specific CENPA-binding ɑ-satellite repeats together with dCas9 fused to a mutant form of KNL1. We designed unique and highly specific sgRNAs for 19 out of 24 chromosomes. Expression of these sgRNAs with KNL1Mut-dCas9 leads to missegregation and induction of gains or losses of the targeted chromosome in cellular progeny with an average efficiency of 8% and 12% for gains and losses, respectively (up to 20%), tested and validated across 9 chromosomes. Using KaryoCreate in colon epithelial cells, we show that chromosome 18q loss, a frequent occurrence in gastrointestinal cancers, promotes resistance to TGFβ, likely due to synergistic hemizygous deletion of multiple genes. Altogether, we describe a novel technology to create and study chromosome missegregation and aneuploidy in the context of cancer and beyond.
2023-08-14 | GSE215842 | GEO
Project description:Aneuploidy, an uneven number of chromosomes, leads to severe developmental defects in mammals and is also a hallmark of cancer. However, whether aneuploidy is a driving cause or a consequence of tumor formation remains controversial. Paradoxically, existing studies based on aneuploid yeast and mouse fibroblasts have shown that aneuploidy is usually detrimental to cellular fitness. Here, we examined the effects of aneuploidy on mouse embryonic stem cells. Using a novel genetic scheme, we generated a series of aneuploid cell lines that each carries an extra copy of single chromosomes and then characterized the traits shared by these cell lines. All the aneuploid cell lines had rapid proliferation rates and enhanced colony formation efficiencies. They were less dependent on growth factors for self-renewal and showed a reduced capacity to differentiate in vitro. Moreover, xenografted aneuploid stem cells formed teratomas more efficiently, with features of neoplastic progression. These findings demonstrate that aneuploidy enhances the self-renewal capacities of stem cells and reduces their differentiation abilities.
2017-02-09 | GSE55499 | GEO
Project description:Aneuploidy, a hallmark of cancer, often arises from whole-chromosomal instability (W-CIN). Many cancers exhibiting W-CIN, however, show no direct insult to the mitotic proteins that ensure proper segregation of chromosomes. This has stimulated interest in identifying defects in non-mitotic processes that might disrupt chromosome behavior in mitosis. Here we show in Saccharomyces cerevisiae that transient re-replication of centromeric DNA, due to deregulation of replication initiation proteins, greatly induces aneuploidy of the rereplicated chromosome. Some of this aneuploidy appears to arise from simple missegregation of both sister chromatids to one daughter cell, indicating that centromeric re-replication can disrupt proper centromere function during mitosis. Another source of aneuploidy appears to be the generation of an extra sister chromatid via homologous recombination, suggesting that centromeric rereplication can trigger breakage and repair events that expand chromosome numbers while preserving chromosome structure. Given the emerging connections between the deregulation of replication initiation proteins and oncogenesis, our findings offer the possibility of a new non-mitotic source of aneuploidy that may be relevant to cancer.
2014-07-25 | GSE55641 | GEO
Project description:Here we provide, for the first time, a longitudinal study of the prevalence, dynamics, and fixation of gross chromosomal rearrangements, including aneuploidy, in the presence and absence of fluconazole during a well-controlled in vitro evolution experiment. While no aneuploidy was detected in any of the no-drug control populations, in all fluconazole-treated populations analyzed, isochromosome 5L [i(5L)] appeared soon after drug exposure, was associated with increased fitness in the presence of drug, and became fixed in independent populations. In two separate cases, larger supernumerary chromosomes composed of i(5L) attached to other chromosome fragments appeared and were later lost during exposure to the drug. Other aneuploidies, particularly trisomies of the smaller chromosomes (Chr3-7), appeared throughout the evolution experiment, and the rapid accumulation of multiple aneuploid chromosomes per cell coincided with the highest resistance to fluconazole.
2009-12-31 | GSE16423 | GEO
Project description:We discovered that wild yeast strains can tolerate extra chromosomes, a condition known as aneuploidy, whereas well-studied laboratory strains cannot. Understanding why some cells can tolerate aneuploidy and others cannot could have far-reaching impact, as for example, 85% of solid tumors are aneuploidy and often benefit from extra chromosomes, and thus identifying mechanisms of aneuploidy sensitization could have therapeutic applications.
2020-01-17 | PXD013847 | Pride