Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nono stimulates the DNA damage response by mediating the induction of Gadd45b [CUT&Run]

ABSTRACT: RNA-binding proteins (RBPs) are frequently deregulated in cancer and emerge as effectors of the DNA damage response (DDR). The non-POU domain-containing octamer-binding protein NONO/p54nrb is a multi-functional RBP that modulates the production and processing of mRNA in unperturbed cells, but also promotes the repair of DNA double-strand breaks (DSBs). Here, we investigate the impact of Nono deletion in the murine cell-based lung cancer model KP (KRasG12D, Trp53-/-). We show that the deletion of Nono impairs the response to DSBs induced by the topoisomerase-II inhibitor etoposide. Nono-deficient KP (KPN) cells display prolonged activation of DSB signaling and an increased amount of DSBs. The defects in the DDR are accompanied with reduced RNAPII promoter occupancy, elevated levels of DNA-RNA-hybrids (R-loops), and attenuated induction of the DDR factor growth arrest and DNA damage inducible beta (Gadd45b). Our data suggest a Nono-mediated, genome-protective crosstalk of the DDR with the RNA metabolism. Our data characterise Gadd45b as putative Nono-dependent effector of the DDR and suggest that Nono mediates a genome-protective crosstalk of the DDR with the RNA metabolism via induction of Gadd45b.

ORGANISM(S): Mus musculus

PROVIDER: GSE250297 | GEO | 2024/06/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Nono stimulates the DNA damage response by mediating the induction of Gadd45b [RNA-seq]

Project description:RNA-binding proteins (RBPs) are frequently deregulated in cancer and emerge as effectors of the DNA damage response (DDR). The non-POU domain-containing octamer-binding protein NONO/p54nrb is a multi-functional RBP that modulates the production and processing of mRNA in unperturbed cells, but also promotes the repair of DNA double-strand breaks (DSBs). Here, we investigate the impact of Nono deletion in the murine cell-based lung cancer model KP (KRasG12D, Trp53-/-). We show that the deletion of Nono impairs the response to DSBs induced by the topoisomerase-II inhibitor etoposide. Nono-deficient KP (KPN) cells display prolonged activation of DSB signaling and an increased amount of DSBs. The defects in the DDR are accompanied with reduced RNAPII promoter occupancy, elevated levels of DNA-RNA-hybrids (R-loops), and attenuated induction of the DDR factor growth arrest and DNA damage inducible beta (Gadd45b). Our data suggest a Nono-mediated, genome-protective crosstalk of the DDR with the RNA metabolism. Our data characterise Gadd45b as putative Nono-dependent effector of the DDR and suggest that Nono mediates a genome-protective crosstalk of the DDR with the RNA metabolism via induction of Gadd45b.

2024-06-04 | GSE250301 | GEO

Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts [APEX2-seq]

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 | GSE236884 | GEO

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

2024-01-16 | GSE236899 | GEO

Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts [mNET]

2024-01-16 | GSE236888 | GEO

Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts [BLISS]

2024-01-16 | GSE236886 | GEO

Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts [4sU-seq]

2024-01-16 | GSE236882 | GEO

Nucleolar detention of NONO shields DNA double-strand breaks form aberrant transcripts

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-localization to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localization is poorly understood. Here we show that the topoisomerase II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-inducible antisense intergenic non-coding RNA (asincRNA) in human cancer cells. Such transcripts originate from distinct nucleolar intergenic spacer regions and form DNA–RNA hybrids to tether NONO to the nucleolus in an RNA recognition motif 1 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 signalling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.

2024-01-16 | GSE233594 | GEO

Nono stimulates the DNA damage response by mediating the induction of Gadd45b

Project description:Nono stimulates the DNA damage response by mediating the induction of Gadd45b

| PRJNA1053326 | ENA

Overexpression of Gadd45b perturbs DNA methylation in mouse dopaminergic neurons

Project description:Age is a major risk factor for neurodegenerative diseases like Parkinson disease, but few studies have explored the contribution of key hallmarks of aging, namely DNA methylation changes and heterochromatin destructuration, in the neurodegenerative process. Here, we investigated the consequences of viral overexpression of Gadd45b, a multifactorial protein involved in DNA demethylation, in the mouse midbrain. Gadd45b overexpression induced global and stable changes in DNA methylation, particularly in introns of genes related to neuronal functions, as well as on LINE-1 transposable elements. This was paralleled by disorganized heterochromatin, increased DNA damage and vulnerability to oxidative stress. LINE-1 de-repression, a potential source of DNA damage, preceded Gadd45b-induced neurodegeneration, whereas prolonged Gadd45b expression deregulated expression of genes related to heterochromatin maintenance, DNA methylation or Parkinson disease. Our data indicates that aging-related alterations contribute to dopaminergic neuron degeneration with potential implications for Parkinson disease.

2021-06-11 | GSE176544 | GEO

Nono stimulates the DNA damage response by mediating the induction of Gadd45b [RNA-seq]

Project description:Nono stimulates the DNA damage response by mediating the induction of Gadd45b [RNA-seq]

| PRJNA1053336 | ENA