PolB_MCP6
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR315828.fastq.gz | Fastqsanger.gz | |||
| ERR315829.fastq.gz | Fastqsanger.gz | |||
| ERR315830.fastq.gz | Fastqsanger.gz | |||
| ERR315831.fastq.gz | Fastqsanger.gz | |||
| ERR315832.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:DNA polymerase β (DNA polymerase beta, POLB) belongs to a member of the DNA polymerase X family, mainly involved in various biological metabolic processes such as eukaryotic DNA replication, DNA damage repair, gene recombination and cell cycle regulation. In this study, the muscle development-related gene POLB was screened by selection signature and RNA-seq analysis, and then validated for the proliferation and apoptosis of bovine primary myocytes. It was also found that overexpression of the POLB gene had a pro-apoptosis effect, but interfering with the expression of the gene had no significant effect on cells. Then the analysis of related apoptotic genes revealed that POLB overexpression affected CASP9 gene expression.
2024-03-29 | GSE262289 | GEO
Project description:Emerging findings suggest that compromised cellular bioenergetics and DNA repair contribute to the pathogenesis of Alzheimer's disease (AD), but their role in disease-defining pathology is unclear. We developed a DNA repair-deficient 3xTgAD/Polb+/- mouse that exacerbates major features of human AD including pTau pathologies, synaptic dysfunction, neuronal death and cognitive impairment. Here we report that 3xTgAD/Polb+/- mice have reduced cerebral NAD+/NADH ratio indicating impaired cerebral energy metabolism, which is normalized by nicotinamide riboside (NR) treatment. NR lessened pTau pathology in both 3xTgAD and 3xTgAD/Polb+/- mice, but had no impact on Abeta accumulation. NR-treated 3xTgAD/Polb+/- mice exhibited reduced DNA damage, neuroinflammation, apoptosis of hippocampal neurons, and increased activity of SIRT3 in the brain. NR improves cognitive function in multiple behavioral tests, and restored hippocampal synaptic plasticity in 3xTgAD mice and 3xTgAD/Polb+/- mice. In general, the deficits and the benefits of NR were greater in 3xTgAD/Polb+/- mice than in 3xTgAD mice. Our findings suggest a pivotal role for cellular NAD+ depletion upstream of neuroinflammation, pTau, DNA damage, synaptic dysfunction and neuronal degeneration in AD. Interventions that bolster neuronal NAD+ levels therefore have potential in AD.
2018-02-26 | GSE109055 | GEO
Project description:We report that the winged helix transcription factor FOXA1 is unexpectedly associated with components of single and double stranded-DNA repair complexes. Biochemical studies and high-throughput approaches validated the hierarchical composition of this FOXA1-nucleated machinery and revealed the dependency on FOXA1 for global targeting of the key repair polymerase POLB. Genome-wide DNA methylomes at single-base resolution demonstrated that FOXA1-DNA repair complex is functionally linked to DNA demethylation in a lineage specific fashion. Loss-of-function studies indicate that a significant portion of FOXA1-bound regions display localized reestablishment of methylation and that the subsets with most consistent hypermethylation are represented by active promoters and enhancers that also exhibit the greatest depletion of POLB following FOXA1 removal. Consistently, forced expression of FOXA1 commits its binding sites to an active DNA demethylation in a POLB dependent manner. Finally, we showed that FOXA1-associated DNA demethylation is tightly coupled with genomic targeting of estrogen receptor and estrogen responsiveness. Together, our results link FOXA1-associated DNA demethylation to its transcriptional pioneering.
2016-06-08 | GSE80808 | GEO
Project description:We recapitulated two main, cellular base excision repair (BER) complexes (herein termed Complex A, comprised of POLB and XRCC1 and Complex B, XRCC1-devoid complexes) by exploiting a separation-of-function mutant of POLB that does not bind to XRCC1, the V303-loop mutant POLB(TM). Cell lines were developed that expressed Flag-tagged-POLB(WT) and Flag-tagged-POLB(TM). To screen for binding partners of POLB or the POLB/XRCC1 complex, anti-Flag M2 affinity gel was used to immunoprecipitate proteins from cell lysates of LN428/Flag-POLB(WT), LN428/Flag-POLB(TM) or LN428/EGFP cells. The immunoprecipitates were loaded on SDS-PAGE gels and proteins were separated from low molecular weight reagents using short gel (~1cm) fractionation. The gels were stained by Coomassie blue. Gel regions were excised as indicated and processed for tryptic digestion. Liquid-chromatography Fourier transform mass spectrometry was used to measure the mass-to-charge (m/z) ratio, retention time, and intensity of more than 100,000 peptide signals that are detected in high-resolution full-scan mass spectra.
2024-04-24 | MSV000094615 | MassIVE
Project description:We report that the winged helix transcription factor FOXA1 is unexpectedly associated with components of single and double stranded-DNA repair complexes. Biochemical studies and high-throughput approaches validated the hierarchical composition of this FOXA1-nucleated machinery and revealed the dependency on FOXA1 for global targeting of the key repair polymerase POLB. Genome-wide DNA methylomes at single-base resolution demonstrated that FOXA1-DNA repair complex is functionally linked to DNA demethylation in a lineage specific fashion. Loss-of-function studies indicate that a significant portion of FOXA1-bound regions display localized reestablishment of methylation and that the subsets with most consistent hypermethylation are represented by active promoters and enhancers that also exhibit the greatest depletion of POLB following FOXA1 removal. Consistently, forced expression of FOXA1 commits its binding sites to an active DNA demethylation in a POLB dependent manner. Finally, we showed that FOXA1-associated DNA demethylation is tightly coupled with genomic targeting of estrogen receptor and estrogen responsiveness. Together, our results link FOXA1-associated DNA demethylation to its transcriptional pioneering.
2016-06-08 | PXD004271 | Pride
Project description:The decline of cognitive function is a feature of normal human aging and is exacerbated in Alzheimer’s disease (AD). DNA repair declines in brain cells during normal aging and even more so in AD. Here we show that experimental reduction in levels of the base excision repair enzyme, DNA polymerase β (Polb) renders neurons vulnerable to age-related dysfunction and degeneration in a mouse model of AD. Whereas 3xTgAD mice exhibit age-related extracellular amyloid b-peptide (Ab) accumulation and cognitive deficits, but no neuronal death, 3xTg/Polb+/- mice accumulates intracellular Ab and neurons die in the hippocampus and cerebral cortex. The DNA repair-deficient 3xTgAD mice exhibited increased DNA strand breaks and apoptotic caspase activation with loss of hippocampal volume, and impaired synaptic plasticity and memory retention. Molecular profiling revealed remarkable similarities in gene expression alterations in brain cells of AD patients and 3xTgAD/Polb+/- mice including multiple abnormalities suggestive of impaired cellular bioenergetics. Our findings demonstrate that a modest decrement in oxidative DNA damage processing is sufficient to render neurons vulnerable to AD-related pathogenic molecular and cellular alterations that result in the dysfunction and death of neurons, and associated cognitive deficits.
2015-01-05 | GSE60911 | GEO
Project description:The decline of cognitive function is a feature of normal human aging and is exacerbated in AlzheimerM-bM-^@M-^Ys disease (AD). DNA repair declines in brain cells during normal aging and even more so in AD. Here we show that experimental reduction in levels of the base excision repair enzyme, DNA polymerase M-NM-2 (Polb) renders neurons vulnerable to age-related dysfunction and degeneration in a mouse model of AD. Whereas 3xTgAD mice exhibit age-related extracellular amyloid b-peptide (Ab) accumulation and cognitive deficits, but no neuronal death, 3xTg/Polb+/- mice accumulates intracellular Ab and neurons die in the hippocampus and cerebral cortex. The DNA repair-deficient 3xTgAD mice exhibited increased DNA strand breaks and apoptotic caspase activation with loss of hippocampal volume, and impaired synaptic plasticity and memory retention. Molecular profiling revealed remarkable similarities in gene expression alterations in brain cells of AD patients and 3xTgAD/Polb+/- mice including multiple abnormalities suggestive of impaired cellular bioenergetics. Our findings demonstrate that a modest decrement in oxidative DNA damage processing is sufficient to render neurons vulnerable to AD-related pathogenic molecular and cellular alterations that result in the dysfunction and death of neurons, and associated cognitive deficits. 4 mouse strains were used in these experiments, the 3xTgAD and Pol M-NM-2 (+/-) mice were bred at the National Institute on Aging (Baltimore, Maryland). The original line 3xTgAD line was generated as described previously (Oddo, et. al 2003) and possess APPswe, PS1M146V, and tauP301L mutations. DNA polymerase beta heterozygous mice, Pol M-NM-2 (+/-), were crossed with the 3xTgAD mice to generate a 3xTgAD/Pol M-NM-2 (+/-) mouse. The Wt strain is C57Bl/6. At 20 months of age these mice were euthanized by cervical dislocation, the brain removed from the skull and dissected into regions of interest, the prefrontal cortex was used for the microarray studies.
2015-01-05 | E-GEOD-60911 | biostudies-arrayexpress