Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia

ABSTRACT: we reported that in the absence of YTHDF2, spermatogonia showed significantly enhanced sensitivity to etoposide and promoted apoptosis, demonstrating that the importance of YTHDF2 in the etoposide-responsive DNA damage response (DDR). Multiple modifications involved in the DDR, some of which recruit repair factors to the sites of DNA damage. N6-methyladenosine (m6A) as a crucial component of the DNA damage repair system responding to DNA lesions. Meanwhile, H3K9me3 has been implicated in DDR, which provides site for DDR factors binding to DNA lesion. Importantly, ablation of Ythdf2 reduced SETDB1 and H3K9me3 levels, and SETDB1 overexpression qualitatively suppressed the DNA damage associated with YTHDF2 loss.

ORGANISM(S): Mus musculus

PROVIDER: GSE217071 | GEO | 2023/12/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia

Project description:YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia

| PRJNA896860 | ENA

Human Fibroblast cells immortalised cells: Control vs DNA damage

Project description:Transcriptional profiling of human fibroblast cells after DNA damage with Camptothecin or Etoposide or Neocarzinostatin Upon DNA damage, the DNA damage response (DDR) elicits a complex signaling cascade, which includes the induction of multiple non-coding RNA species. Recently long non-coding RNAs (lncRNAs) have been shown to contribute to DDR by regulating gene expression. However, very little is known about the role that lncRNAs play in regulating DNA Repair. Using a genome-wide microarray screen we identified a novel ubiquitously expressed lncRNA, DDSR1 (DNA damage-sensitive RNA 1), which is induced upon DNA damage by several DNA double-strand break (DSB) agents. Two-condition experiment, Control vs. DNA damage human fibroblast cells. No Replicates, DNA damage was induced with either Camptothecin or Etoposide or Neocarzinostatin, Total RNA or Nuclear RNA was profiled.

2015-09-01 | E-GEOD-67062 | biostudies-arrayexpress

Setdb1 is essential for meiotic sex chromosome inactivation in mice

Project description:Meiotic synapsis and recombination ensure correct homologous segregation and genetic diversity. Asynapsed homologues are transcriptionally inactivated by meiotic silencing, which serves a surveillance function and in males drives meiotic sex chromosome inactivation. Silencing depends on the DNA damage response (DDR) network, but how DDR proteins engage repressive chromatin marks is unknown. We identify the histone H3-lysine-9 methyltransferase SETDB1 as the bridge linking the DDR to silencing in male mice. At the onset of silencing, X-chromosome H3K9 trimethylation (H3K9me3) enrichment is downstream of DDR factors. Without Setdb1, the X chromosome accrues DDR proteins but not H3K9me3. Consequently, sex chromosome remodelling and silencing fails, causing germ cell apoptosis. Our data implicate TRIM28 in linking the DDR to SETDB1, and uncover additional factors with putative meiotic XY-silencing functions. Furthermore, we show that SETDB1 imposes timely expression of meiotic and post-meiotic genes. Setdb1 thus unites the DDR network, asynapsis and meiotic chromosome silencing.

2018-11-01 | GSE107671 | GEO

Human Fibroblast cells immortalised cells: Control vs DNA damage

2015-09-01 | GSE67062 | GEO

Metabolic responses induced by DNA damage and poly (ADP-ribose) polymerase (PARP) inhibition in MCF-7 cells

Project description:Genomic instability is one of the hallmarks of cancer. Several chemotherapeutic drugs and radiotherapy induce DNA damage to prevent cancer cell replication. Cells in turn activate different DNA damage response (DDR) pathways to either repair the damage or induce cell death. These DDR pathways also elicit metabolic alterations which can play a significant role in the proper functioning of the cells. The understanding of these metabolic effects resulting from different types of DNA damage and repair mechanisms is currently lacking. In this study, we used NMR metabolomics to identify metabolic pathways which are altered in response to different DNA damaging agents. By comparing the metabolic responses in MCF-7 cells, we identified the activation of poly (ADP-ribose) polymerase (PARP) in methyl methanesulfonate (MMS)-induced DNA damage. PARP activation led to a significant depletion of NAD+. PARP inhibition using veliparib (ABT-888) was able to successfully restore the NAD+ levels in MMS-treated cells. In addition, double strand break induction by MMS and veliparib exhibited similar metabolic responses as zeocin, suggesting an application of metabolomics to classify the types of DNA damage responses. This prediction was validated by studying the metabolic responses elicited by radiation. Our findings indicate that cancer cell metabolic responses depend on the type of DNA damage responses and can also be used to classify the type of DNA damage.

2015-08-01 | MTBLS177 | MetaboLights

SUMO-2 Orchestrates Chromatin Modifiers in Response to DNA Damage

Project description:Small Ubiquitin-like Modifiers play critical roles in the DNA Damage Response (DDR). To increase our understanding of SUMOylation in the mammalian DDR, we employed a quantitative proteomics approach to identify dynamically regulated SUMO-2 conjugates and modification sites upon treatment with the DNA damaging agent MMS. We have uncovered a dynamic set of 20 upregulated and 33 downregulated SUMO-2 conjugates, and 755 SUMO-2 sites, of which 362 were dynamic in response to MMS. In contrast to yeast, where a response is centered on homologous recombination, we identified dynamically SUMOylated interaction networks of chromatin modifiers, transcription factors, DNA repair factors and nuclear body components. SUMOylated chromatin modifiers include JARID1B/KDM5B, JARID1C/KDM5C, p300, CBP, PARP1, SetDB1 and MBD1. Whereas SUMOylated JARID1B was ubiquitylated by the SUMO-targeted ubiquitin ligase RNF4 and degraded by the proteasome in response to DNA damage, JARID1C was SUMOylated and recruited to the chromatin to demethylate histone H3K4.

2015-03-16 | PXD001810 | Pride

Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts [CUT&RUN]

Project description:RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54nrb marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localisation to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localisation is poorly understood. Here we show that the topoisomerase-II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-induced nucleolar antisense RNAs (diNARs) in human cancer cells. diNARs originate from distinct nucleolar intergenic spacer regions and form DNA-RNA hybrids to tether NONO to the nucleolus in ab RRM1 domain-dependent manner. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of a subset of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signaling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.

2024-01-16 | GSE236899 | GEO