INTS6 controls DNA:RNA hybrids autoregulation at double-strand break through Senataxin
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1034504 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26625311_1.fastq.gz | Fastqsanger.gz | |||
| SRR26625311_2.fastq.gz | Fastqsanger.gz | |||
| SRR26625312_1.fastq.gz | Fastqsanger.gz | |||
| SRR26625312_2.fastq.gz | Fastqsanger.gz | |||
| SRR26625313_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
Similar Datasets
Project description:The fidelity of transcription is essential for genome stability, especially when DNA damage happens. However, how the transcription cycle is regulated remains unknown. Here, we found that INTS6 is a fundamental player, which recruits PP2A to double-strand breaks (DSBs) and functions together with senataxin (SETX). The in-depth insight of ChromeRNA-seq shows that INTS6 is not only involved in global transcription termination but also the de novo transcription termination. Therefore, INTS6 is a great target for future translational studies.
2024-10-18 | GSE246729 | GEO
Project description:RNA-DNA hybrids are a major internal cause of DNA damage within cells, and their degradation by RNAse H enzymes is important for maintaining genomic stability. Here, we identified an unexpected role for RNA-DNA hybrids and RNase H enzymes in DNA repair. Using a site-specific DNA double-stranded break (DSB) system in Schizosaccharomyces pombe, we showed that RNA-DNA hybrids form as part of the homologous recombination (HR)-mediated DSB repair process and RNase H enzymes are essential for their degradation and efficient completion of DNA repair. Deleting RNase H stabilizes RNA-DNA hybrids around DSB sites and strongly impairs recruitment of the ssDNA-binding RPA complex. In contrast, overexpressing RNase H1 destabilizes these hybrids, leading to excessive strand resection and RPA recruitment, and to severe loss of repeat regions around DSBs. Our study challenges the existing model of HR-mediated DSB repair, and reveals a surprising role for RNA-DNA hybrids in maintaining genomic stability.
2016-10-28 | GSE84882 | GEO
Project description:RNA-DNA hybrids are a major internal cause of DNA damage within cells, and their degradation by RNAse H enzymes is important for maintaining genomic stability. Here, we identified an unexpected role for RNA-DNA hybrids and RNase H enzymes in DNA repair. Using a site-specific DNA double-stranded break (DSB) system in Schizosaccharomyces pombe, we showed that RNA-DNA hybrids form as part of the homologous recombination (HR)-mediated DSB repair process and RNase H enzymes are essential for their degradation and efficient completion of DNA repair. Deleting RNase H stabilizes RNA-DNA hybrids around DSB sites and strongly impairs recruitment of the ssDNA-binding RPA complex. In contrast, overexpressing RNase H1 destabilizes these hybrids, leading to excessive strand resection and RPA recruitment, and to severe loss of repeat regions around DSBs. Our study challenges the existing model of HR-mediated DSB repair, and reveals a surprising role for RNA-DNA hybrids in maintaining genomic stability.
2016-10-28 | GSE80398 | GEO
Project description:Neurodegeneration in the human population is often associated with loss of protein homeostasis that is driven by accumulation of specific aggregated proteins. Here we investigate whether deficiency in Senataxin, an RNA-DNA helicase associated with cerebellar ataxia and ALS, induces destabilization of intrinsically disordered proteins as we previously found with Ataxia-telangiectasia (A-T) cells and tissue. We find that Senataxin loss does generate protein aggregates but, unlike in A-T, these are associated with the nucleolus and are independent of oxidative stress and PARP activity. Non-coding RNA expression from the intergenic spacer region of ribosomal DNA is induced in the absence of Senataxin and drives the association and aggregation of many proteins known to be prone to aggregation in neurodegenerative disease. Both non-coding RNAs and protein aggregates are eliminated by overexpression of RNaseH1, implicating RNA-DNA hybrids as the key driver of these outcomes. We find that hybrids are high in the absence of Senataxin at intergenic sites, not at annotated protein-coding genes; these include sites of Senataxin binding in the genome, ribosomal DNA, and peri-centromeric regions. These findings suggest that destabilization of the proteome is driven by Senataxin loss and that RNA-DNA hybrids and non-coding RNAs play a critical role in this process.
2024-05-06 | GSE240664 | GEO
Project description:DNA Double Strands Breaks (DSBs) are highly detrimental since they can lead to mutations and chromosomes rearrangements (amplification, deletion, translocation and chromosome loss). Here, we set to assess the role of senataxin, a RNA:DNA helicase involved in the regulation of transcription and the maintenance of genome integrity, at sites of DNA Double Strand Breaks. We performed ChIP-Seq mapping of senataxin before and after damage, genome-wide DNA:RNA hybrids (DRIP) mapping before and after damage. We also performed RNA-Seq and RNA pol II mapping (total and phosphorylated on serine 2 of the CTD) by ChIP-Seq in undamaged cells to discriminate between damage in active versus inactive regions.
2018-02-20 | E-MTAB-6318 | biostudies-arrayexpress
Project description:Transient RNA-DNA Hybrids Are Required for Efficient Double-Strand Break Repair
| PRJNA335431 | ENA
Project description:Here we analysed the role of yeast Senataxin (Sen1) in coordinating replication with transcription and in protecting genome integrity. Senataxin is mutated in the two severe neurodegenerative diseases AOA2 and ALS4. We show that a fraction of Sen1/Senataxin DNA/RNA helicase associates with replication forks and protects the integrity of those fork encountering highly expressed RNAPII genes. sen1 mutants accumulate aberrant DNA structures and RNA-DNA hybrids while forks clash head-on with RNAPII transcription units and counteract recombinogenic events and accumulation of checkpoint signals. Nrd1, which acts togheter with Sen1 in trascription temination, is not recruited at replication forks. nrd1 mutants does not display replication defects, high genome instability and checkpoint activation observed in sen1 mutants The Sen1 function in replication can be therefore separable from its role in RNA processing. We propose a role for Sen1/Senataxin during chromosome replication in facilitating replisome progression across RNAPII transcribed genes thus preventing DNA-RNA hybrids accumulation when forks encounter nascent transcripts on the lagging strand template.
2012-11-09 | GSE39139 | GEO
Project description:Here we analysed the role of yeast Senataxin (Sen1) in coordinating replication with transcription and in protecting genome integrity. Senataxin is mutated in the two severe neurodegenerative diseases AOA2 and ALS4. We show that a fraction of Sen1/Senataxin DNA/RNA helicase associates with replication forks and protects the integrity of those fork encountering highly expressed RNAPII genes. sen1 mutants accumulate aberrant DNA structures and RNA-DNA hybrids while forks clash head-on with RNAPII transcription units and counteract recombinogenic events and accumulation of checkpoint signals. Nrd1, which acts togheter with Sen1 in trascription temination, is not recruited at replication forks. nrd1 mutants does not display replication defects, high genome instability and checkpoint activation observed in sen1 mutants The Sen1 function in replication can be therefore separable from its role in RNA processing. We propose a role for Sen1/Senataxin during chromosome replication in facilitating replisome progression across RNAPII transcribed genes thus preventing DNA-RNA hybrids accumulation when forks encounter nascent transcripts on the lagging strand template. Chip on chip analysis was carried out as described (Bermejo et al., 2011), employing anti-Flag monoclonal antibody M2 (Sigma-Aldrich) Labelled probes were hybridized to Affymetrix S.cerevisiae Tiling 1.0 (P/N 900645) arrays and processed with TAS software.
2012-11-09 | E-GEOD-39139 | biostudies-arrayexpress
Project description:The microRNA biogenesis enzyme Drosha was found to be important for DNA repair and this function appears to be distinct to its role in miRNA-mediated repression. Novel small RNAs were reported previously to be produced from the sequences around a DNA break. Utilising an endonuclease system (AsiSI) we were unable to detect such small RNA around 100 cuts within the endogenous genome. Sequencing of R-loops (DNA:RNA hybrids) was performed and an increase in R-loop formation was observed around many DNA break sites. Loss of Drosha appears to perturb this damage dependent formation of R-loops. RNase H1 over-expression appears to reduce repair at these break sites. Drosha appears to be important for facilitating R-loop formation at DNA break sites to aid in the repair process.
2018-02-18 | GSE97648 | GEO
Project description:Class switch recombination generates antibody distinct isotypes critical to a robust adaptive immune system and defects are associated with auto-immune disorders and lymphomagenesis. Transcription is required during class switch to recruit the cytidine deaminase AID—an essential step for the formation of DNA doublestrand breaks—and strongly induces the formation of R loops within the immunoglobulin heavy chain locus. However, the impact of R loops on double-strand break formation and repair during class switch recombination remains unclear. Here we report that cells lacking two enzymes involved in R loop removal— Senataxin and RNase H2—exhibit increased R loop formation and genome instability at the immunoglobulin heavy chain locus without impacting class switch recombination efficiency, transcriptional activity, or AID recruitment. Senataxin and RNase H2-deficient cells also exhibit increased insertion mutations at switch junctions, a hallmark of alternative end joining. Importantly, these phenotypes were not observed in cells lacking Senataxin or RNase H2B alone. We propose that Senataxin acts redundantly with RNase H2 to mediate timely R loop removal, promoting efficient repair while suppressing AID-dependent genome instability and insertional mutagenesis.
2022-12-14 | GSE201210 | GEO