Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-Seq profiling of ERCC1-XPF DNA repair defect (Er1F/-) versus wild type (Er1F/+) macrophages

ABSTRACT: DNA damage and metabolic disorders are intimately linked with premature disease onset but the underlying mechanisms remain poorly understood. Persistent DNA damage accumulation in tissue-infiltrating macrophages carrying an ERCC1-XPF DNA repair defect (Er1F/-) riggers Golgi dispersal, dilation of endoplasmic reticulum, autophagy and exosome biogenesis leading to the secretion of extracellular vesicles (EVs) in vivo and ex vivo.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: George Garinis

PROVIDER: E-MTAB-8439 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Transcription profiling of liver from wild type or Ercc1 mutant mice

Project description:The XPF-ERCC1 endonuclease is required for repair of helix-distorting DNA damage and interstrand crosslinks. Here we have engineered a severe mutation in Ercc1 gene (in which the last 7 amino acids are missing; named as "Ercc1-delta") leading to extreme sensitivity to DNA crosslinks and progeria.To investigate whether a disturbance in growth and metabolism could explain the pronounced accelerated organismal deterioration seen in Ercc1 delta mice, we evaluated the liver transcriptome of 16-week-old wt and mutant mice (n=6). At this age, the Ercc1-delta mice have not yet become cachectic.

2008-06-01 | E-MEXP-1503 | biostudies-arrayexpress

Tissue-infiltrating macrophages mediate an exosome-based metabolic reprogramming upon DNA damage

Project description:DNA damage and metabolic disorders are intimately linked with premature disease onset but the underlying mechanisms remain poorly understood. Here, we show that persistent DNA damage accumulation in tissue-infiltrating macrophages carrying an ERCC1-XPF DNA repair defect (Er1F/-) riggers Golgi dispersal, dilation of endoplasmic reticulum, autophagy and exosome biogenesis leading to the secretion of extracellular vesicles (EVs) in vivo and ex vivo. Macrophage-derived EVs accumulate in Er1F/- animal sera and are secreted in macrophage media after DNA damage. The Er1F/- EV cargo is taken up by recipient cells leading to an increase in insulin-independent glucose transporter levels, enhanced cellular glucose uptake, higher cellular oxygen consumption rate and greater tolerance to glucose challenge in mice. We find that high glucose in EV-targeted cells triggers pro-inflammatory stimuli via mTOR activation. This, in turn, establishes chronic inflammation and tissue pathology in mice with important ramifications for DNA repair-deficient, progeroid syndromes and aging.

2019-11-06 | PXD015727 | Pride

Identify the protein partners of Ercc1 in DNA damage progeria in MEFs

Project description:ERCC1 is a DNA endonuclease participating in the Nucleotide Excision Repair (NER) pathway. Its functionality is related to XPF; the two proteins work as a heterodimer to incise the 5 of a 30-mer that contains the damaged nucleotide and remove the fragment together with XPG. Apart from NER deficiency, mutated Ercc1 in mice and humans causes a series of progeroid symptoms (premature ageing). We hypothesize that there are undescribed functions of ERCC1, possibly in transcriptional regulation that contribute to the development of the striking phenotypes observed. The aim is to identify previously uncharacterized protein partners of ERCC1 that might contribute to our understanding of its differential roles during DNA damage-driven progeria.

2023-10-04 | PXD017063 | Pride

Effect of LPS and the glucocorticoid dexamethasone on the mouse Bone Marrow Derived Macrophage Proteome

Project description:The concentrations and copy number of proteins in the mouse Bone Marrow Derived proteome was determined for control, 10 ng/mL LPS stimulation, and LPS stimulation plus the addition of 100 nM dexamethasone, after an incubation for 24 hours and with four biological replicates for each condition. Over 6000 proteins were detected, 410 of which were upregulated by LPS (> 1.5-fold increase, adjusted p value < 0.05). 125 of these LPS-induced proteins were significantly regulated by Dexamethason > 1.5 fold 899 increase or decrease, adjusted p value <0.05).

2024-01-26 | PXD041375 | Pride

Identification of a new XPF-ERCC1-like complex important for meiotic crossovers production

Project description:Proteins of the XPF-ERCC1 complex family play roles in DNA repair. Known members (four in mammals, two in budding yeast) recognize branched DNA structures and most bear nuclease activity. Here, we identified a new XPF-ERCC1-like complex important for meiotic crossovers production. Through a proteomic screen, we found that Zip2 and Spo16, two proteins important for CO formation in budding yeast, form a complex and share structural similarities with XPF-ERCC1. Zip2 XPF domain is important for CO formation and, in complex with Spo16, preferentially binds branched DNA molecules. However, Zip2-Spo16 lacks endonucleolytic activity. This suggests that Zip2-Spo16 works as a structural module that recognizes and stabilizes joint molecules to ensure CO formation. Moreover, Zip2-Spo16 forms a complex (called ZZS) with Zip4, another protein important for CO formation, which directly interacts with components of the chromosome axis, providing a link between recombination intermediates and the underlying chromosome structure.

2018-04-10 | PXD007735 | Pride

SLX4 and SLX4IP TAP-MS - SLX4IP acts with SLX4 and XPF-ERCC1 to promote interstrand crosslink repair

Project description:Interstrand crosslinks (ICLs) are highly toxic DNA lesions, which are repaired via a complex process that requires the coordination of several DNA repair pathways. Defects in ICL repair result in Fanconi anemia (FA), which is diagnosed with bone marrow failure, development abnormalities and high incidence of malignancies. SLX4, which is also known as FANCP, acts as a scaffold protein in coordinating multi-endonucleases that function in unhooking ICLs, resolving homologous recombination intermediates, and perhaps also removing unhooked ICLs. To reveal the underlying mechanism for the involvement of SLX4IP in ICL repair, we tagged SFB to the C terminus of SLX4IP and performed tandem affinity purification and mass spectrometry analysis as outlined above. We found SLX4 and XPF-ERCC1 at the top of the list of SLX4IP-binding proteins. We also identified some other potential SLX4IP interacting proteins, such as PASK, AJUBA, LRP4 and TRIM26, but none of them has been previously indicated to participate in DNA repair. SLX4 and XPF-ERCC1 are the major SLX4IP-interacting proteins, with or without MMC treatment. SLX4 has been shown to coordinate with XPF-ERCC1 and participate in the unhooking of ICLs during the repair process. The binding of SLX4IP to both SLX4 and XPF-ERCC1 intrigued us to further investigate whether SLX4IP plays a role in regulating SLX4-XPF-ERCC1 interaction.

2019-09-13 | PXD012521 | Pride

Mouse WT vs. A20 KO BMDM differential proteomics

Project description:A20 is a negative regulator of NF-κB signaling, crucial to control inflammatory responses and ensure tissue homeostasis. A20 is thought to restrict NF-κB activation both by its ubiquitin-editing activity as by non-enzymatic activities. Besides its role in NF-κB signaling, A20 also acts as a protective factor inhibiting apoptosis and necroptosis. Because of the ability of A20 to both ubiquitinate and deubiquitinate substrates and its involvement in many cellular processes, we hypothesized that deletion of A20 might generally impact on protein levels, thereby disrupting cellular processes. We performed a differential proteomics study of bone marrow derived macrophages (BMDMs) from control and myeloid-specific A20 knockout mice, both in untreated conditions and after LPS and TNF treatment, and demonstrate proteome-wide changes in protein expression upon A20 deletion. Several inflammatory proteins are up-regulated in the absence of A20, even without an inflammatory stimulus. Depending on the treatment and the time, more proteins are regulated. Together these changes may affect multiple signaling pathways disturbing tissue homeostasis and inducing (autoimmune) inflammation, as suggested by genetic studies in patients.

2018-05-15 | PXD008726 | Pride

ERCC1-XPF Cooperates with CTCF and the Cohesin to Facilitate the Developmental Silencing of Imprinted Genes

Project description:Inborn defects in DNA repairare associated with complex developmental disorders whose causal mechanisms are poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development. Loss of Ercc1or exposure to mitomycin C triggers the localization of CTCF to heterochromatin, the dissociation of the CTCF-cohesin complex and ATRXfrom promoters and ICRs,altered histone marks and the aberrant developmental expression of imprinted genes without altering DNA methylation. We propose that ERCC1-XPF cooperates with CTCF and the cohesinto facilitatet he developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders.

2017-04-04 | PXD005897 | Pride

MiRNA expression profiling or ERCC1 deficient and control mouse lineage negative bone marrow cells

Project description:MiRNA expression differences induced by ERCC1 deficiency.

2015-04-09 | E-MTAB-3298 | biostudies-arrayexpress

Gene expression profiling or ERCC1 deficient and control mouse lineage negative bone marrow cells

Project description:Transcriptome differences induced by ERCC1 deficiency.

2015-04-09 | E-MTAB-3297 | biostudies-arrayexpress