Transcriptomic profiling of Arabidopsis DNA POLYMERASE EPSILON CATALYTIC SUBUNIT A (AtPOL2a) and B (AtPOL2b) mutants
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR476702_1.fastq.gz | Fastqsanger.gz | |||
| ERR476702_2.fastq.gz | Fastqsanger.gz | |||
| ERR476703_1.fastq.gz | Fastqsanger.gz | |||
| ERR476703_2.fastq.gz | Fastqsanger.gz | |||
| ERR476704_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 10 |
Similar Datasets
Project description:DNA polymerase epsilon (Pol epsilon) plays multiple roles in genome duplication and its catalytic subunit POLE suppresses tumorigenesis in humans. Despite its importance, we have limited understanding of Pol epsilon functional mechanisms and how its loss-of-function affects the evolution of cancer genomes. To address this issue, we used the budding yeast ortholog Pol2 to model cancer-associated POLE mutations that affect an uncharacterized yet highly conserved Pol2/POLE family-specific region. Analysis of pol2 mutants revealed an unexpected role for this region in the incorporation of Pol epsilon into the pre-loading complex during replisome assembly. Cellular and reconstitution experiments further identified a separate role for this region in promoting Pol epsilon polymerase activity. Unlike previously reported POLE mutations leading to hypermutation in cancer cells, the examined pol2 variants increase gross chromosomal rearrangements but not mutation rates. Our findings thus suggest that the Pol epsilon catalytic core integrates replisome assembly and DNA polymerization functions and that POLE tumor suppressive roles likely extend beyond limiting replication errors.
2020-03-29 | GSE132450 | GEO
Project description:The CIC::DUX4 oncoprotein maintains DNA integrity through direct regulation of the catalytic subunit of DNA polymerase epsilon (POLE).
| PRJNA1172903 | ENA
Project description:Transcription factor (TF) fusion oncoproteins represent cancer specific alterations that arise from chromosomal rearrangements. Through target gene recognition, TF fusions can disseminate transcriptional responses that collectively work to drive tumorigenesis. Thus, identifying the molecular targets that operate as a disease driving network can potentially uncover key actionable dependencies. We have taken this strategy to dissect the underlying biological mechanism by which CIC::DUX4, a fusion oncoprotein associated with dismal outcomes, drives sarcomagenesis. We and others have defined a CIC::DUX4 fusion mediated network that dysregulates cell-cycle and DNA replication checkpoints. Specifically, CIC::DUX4-mediated CCNE1 upregulation compromises the G1/S transition leading to high DNA replication stress and conferring a dependence on the G2/M checkpoint kinase, WEE1. Thus, WEE1 provides a molecular brake to enable effective DNA repair prior to mitotic entry. Importantly, the mechanism by which CIC::DUX4 regulates DNA repair remains unknown. Here we show that the catalytic subunit of DNA polymerase epsilon (POLE) is essential for DNA integrity and cellular division in CIC::DUX4 sarcoma. Mechanistically, POLE loss increases DNA damage and induces p21-mediated cellular senescence to limit CIC:DUX4 mediated tumor growth in vitro and tumor formation in vivo. Altogether, we credential POLE as a CIC::DUX4 target and further characterize a functional network through which CIC::DUX4 operates to drive tumor progression and survival.
2024-10-16 | GSE279467 | GEO
Project description:The evolutionary and functional importance of AtPOL2a and AtPOL2b allowed us to study these two genes in-depth at a molecular level. Here we report transcriptomes of single gene mutants of AtPOL2s at a global scale using the Illumina HiSeq 2000 platform. This includes a homozygous T-DNA mutant line of AtPOL2a (NASC accession number: N676289) and three homozygous T-DNA lines of AtPOL2b (NASC accession numbers: N859810, N501413 and N859809), confirmed through PCR to have insertions spanning across different positions of the genes. The transcript levels of genes were compared between wild type and AtPOL2 mutants to gain insight into potential interactions at a transcriptomic level.
2016-01-31 | E-MTAB-2465 | biostudies-arrayexpress
Project description:Yeast Saccharomyces cerevisiae has been widely used as a model system for studying genome instability. Here, a heterozygous diploid S. cerevisiae strain DZP2 was generated to determine the genomic alterations induced by DNA polymerase ε. The expression of POL2 was regulated by the GAL1 promoter. In combination of a custom SNP microarray, the patterns of chromosomal instability induced by low Pol ε could be explored at a whole genome level in DZP2. Using this system, we found hundreds-fold higher rate of genomic alterations, including aneuploidy, loss of heterozygosity (LOH), and chromosomal rearrangement. DNA polymerase ε (Pol ε) is one of the three replicative eukaryotic DNA polymerases. Pol ε deficiency leads to genomic instability and multiple human diseases. Here, we explored global genomic alterations in yeast strains with reduced expression of POL2, the gene that encodes the catalytic subunit of Pol ε. Using whole-genome SNP microarray and sequencing, we found that low levels of Pol ε elevated the rates of mitotic recombination and chromosomal aneuploidy by two orders of magnitude. Strikingly, low levels of Pol ε resulted in a contraction of the number of repeats in the rDNA cluster and reduced the length of telomeres. These short telomeres led to an elevated frequency of break-induced replication, resulting in terminal loss of heterozygosity. In addition, low levels of Pol ε increased the rate of single-base mutations by 13-fold by a Pol ζ-dependent pathway. Finally, the patterns of genomic alterations caused by low levels of Pol ε were different from those observed in strains with low levels of the other replicative DNA polymerases Pol α and Pol δ, providing further insights into the different roles of the B-family DNA polymerases in maintaining genomic stability.
2021-10-07 | GSE185365 | GEO
Project description:Yeast Saccharomyces cerevisiae has been widely used as a model system for studying genome instability. Here, a heterozygous diploid S. cerevisiae strain DZP2 was generated to determine the genomic alterations induced by DNA polymerase ε. The expression of POL2 was regulated by the GAL1 promoter. In combination of a custom SNP microarray, the patterns of chromosomal instability induced by low Pol ε could be explored at a whole genome level in DZP2. Using this system, we found hundreds-fold higher rate of genomic alterations, including aneuploidy, loss of heterozygosity (LOH), and chromosomal rearrangement. DNA polymerase ε (Pol ε) is one of the three replicative eukaryotic DNA polymerases. Pol ε deficiency leads to genomic instability and multiple human diseases. Here, we explored global genomic alterations in yeast strains with reduced expression of POL2, the gene that encodes the catalytic subunit of Pol ε. Using whole-genome SNP microarray and sequencing, we found that low levels of Pol ε elevated the rates of mitotic recombination and chromosomal aneuploidy by two orders of magnitude. Strikingly, low levels of Pol ε resulted in a contraction of the number of repeats in the rDNA cluster and reduced the length of telomeres. These short telomeres led to an elevated frequency of break-induced replication, resulting in terminal loss of heterozygosity. In addition, low levels of Pol ε increased the rate of single-base mutations by 13-fold by a Pol ζ-dependent pathway. Finally, the patterns of genomic alterations caused by low levels of Pol ε were different from those observed in strains with low levels of the other replicative DNA polymerases Pol α and Pol δ, providing further insights into the different roles of the B-family DNA polymerases in maintaining genomic stability.
2021-10-07 | GSE185364 | GEO
Project description:DNA replication requires the faithful propagation of both genetic and epigenetic information. There is evidence that DNA polymerases play a role in transcriptional silencing, but the extent of their contribution and how it relates to heterochromatin maintenance is unclear. Analyzing a new hypomorphic pol2a mutant allele, we find that POL2A, the catalytic subunit of the DNA polymerase epsilon, maintains heterochromatin silencing and nuclear organization. Here, we profiled the DNA methylation landscape using BS-seq in various pol2a mutant alleles in Arabidopsis, in combination or not with other silencing and methyltransferase mutants. We also generated methylomes of wild-type and pol2a mutants exposed to hydroxyurea, to explore the consequences of replicative stress onto DNA methylation maintenance.
2020-06-04 | E-MTAB-8940 | biostudies-arrayexpress
Project description:DNA replication requires the faithful propagation of both genetic and epigenetic information. There is evidence that DNA polymerases play a role in transcriptional silencing, but the extent of their contribution and how it relates to heterochromatin maintenance is unclear. Analyzing a new hypomorphic pol2a mutant allele, we find that POL2A, the catalytic subunit of the DNA polymerase epsilon, maintains heterochromatin silencing and nuclear organization. We also found that POL2 inhibits DNA methylation and histone H3 lysine 9 methylation, which both correlate with 24-nucleotide small RNA accumulation. In this experiment, we sequenced small-RNA libraries generated from immature inflorescences of pol2a-10 and pol2a-12 mutants and wild-type plants.
2020-06-04 | E-MTAB-8938 | biostudies-arrayexpress
Project description:DNA replication requires the faithful propagation of both genetic and epigenetic information. There is evidence that DNA polymerases play a role in transcriptional silencing, but the extent of their contribution and how it relates to heterochromatin maintenance is unclear. To get a better understanding of the role of POL2A, the catalytic subunit of the DNA polymerase epsilon, into maintaining heterochromatin silencing, we performed mRNA-seq on Arabidopsis plants carrying a new hypomorphic pol2a mutation. We deepened our analysis by profiling transcriptomes of other silencing mutants or combinations of pol2a with other mutations.
2020-06-04 | E-MTAB-8939 | biostudies-arrayexpress
Project description:DNA replication requires the faithful propagation of both genetic and epigenetic information. There is evidence that DNA polymerases play a role in transcriptional silencing, but the extent of their contribution and how it relates to heterochromatin maintenance is unclear. Analyzing a new hypomorphic pol2a mutant allele, we find that POL2A, the catalytic subunit of the DNA polymerase epsilon, maintains heterochromatin silencing and nuclear organization. We also found that POL2A inhibits DNA methylation. Using ChIP-seq in wild-type and pol2a mutants, we analyzed how this related to changes in heterochromatic histone modifications (H3K27me1, H3K27me3, H3K9me2) and H2A.W heterochromatic histone variant.
2020-10-18 | E-MTAB-9046 | biostudies-arrayexpress