Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Senataxin associates with replication forks to protect fork integrity across RNAPII transcribed genes

ABSTRACT: 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.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Rodrigo Bermejo

PROVIDER: E-GEOD-39139 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Senataxin associates with replication forks to protect fork integrity across RNAPII transcribed genes

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

The Sen1 Helicase Prevents Spurious Transcription by Controlling Genome-Wide Transcription Termination by RNAPII

Project description:RNA Polymerase II (RNAPII) termination for transcripts containing a polyadenylation signal (PAS) is thought to differ mechanistically from termination for PAS-independent RNAPII transcripts such as sn(o)RNAs. In a screen for factors required for PAS-dependent termination, we identified Sen1, a putative helicase known primarily for its role in PAS-independent termination. We show that Sen1 is required for termination on hundreds of protein-coding genes and suppresses cryptic transcription from nucleosome-free regions on a genomic scale. These effects often overlap with but are also often distinct from those caused by Nrd1 depletion, which also impacts termination of protein-coding and cryptic transcripts, including many genic antisense transcripts. Sen1 controls termination through its helicase activity and stimulates recruitment of factors previously implicated in both PAS-dependent (Rna14, Rat1) and PAS-independent (Nrd1) termination. Thus, RNAPII termination for both protein-coding genes and cryptic transcripts is dependent on multiple pathways. The 2 RNAPII datasets were produced in duplicates and the Sen1 and Nrd1 datasets in triplicates (all IP/Input).

2011-06-01 | E-GEOD-19015 | biostudies-arrayexpress

The Sen1 Helicase Prevents Genome-Wide Spurious Transcription by Controlling Transcription Termination by RNAPII

Project description:It is currently believed that termination by RNAPII occurs differently depending whether a transcript contains or lacks a polyadenylation signal (PAS). By screening for factors deficient for PAS-dependent termination in an in vivo reporter assay, we identified Sen1, a putative helicase mainly known for its role in PAS-independent termination of snoRNAs. We show for the first time that Sen1 regulates transcription termination at protein-encoding genes genome-wide. As well, we show that Sen1 suppresses cryptic transcription genome-wide, besides being required for termination of most snoRNAs. We provide evidence that Sen1 controls termination through its helicase activity and by effectively recruiting to chromatin, factors implicated in PAS-dependent (Rna14 and Rat1) or PAS-independent termination (Nrd1). Importantly, we demonstrate that the effect on transcription termination of Sen1 and Nrd1, although similar, differ quantitatively and qualitatively. Our results suggest that in yeast, termination by RNAPII at protein encoding-genes makes use of redundant pathways.

2010-01-01 | GSE17559 | GEO

Sen1 and Rrm3 ensure permissive topological conditions for replication termination [ChIP-seq]

Project description:Replication forks terminate at TERs and telomeres. Forks that converge or encounter transcription generate topological stress. Combining genetic, genomic and imaging approaches we found that Rrm3hPif1 and Sen1hSenataxin helicases assist termination at TERs, Sen1 at telomeres. rrm3 and sen1 are synthetic lethal, fail to terminate replication exhibiting lagging chromosomes and fragility at TERs and telomeres. sen1 rrm3 build up RNA-DNA hybrids at TERs, sen1 accumulates RNPII at TERs and telomeres. Double mutants exhibit X-shaped gapped or reversed converging forks. Rrm3 and Sen1 restrain Top1 and Top2 activities, preventing toxic accumulation of positive supercoil at TERs and telomeres. We suggest that Rrm3 and Sen1 coordinate the activities of fork-associated Top1 and Top2 with those of gene loop-associated Top1 and Top2 by preventing DNA and RNA polymerases slowing down when forks encounter transcription head-on or codirectionally, respectively. Hence Rrm3 and Sen1 are essential to generate permissive topological conditions for replication termination.

2022-10-11 | GSE214925 | GEO

Sen1 and Rrm3 ensure permissive topological conditions for replication termination [ChIP-chip]

2022-10-11 | GSE214908 | GEO

High-resolution mapping of transcribing RNAPIII by CRAC upon depletion of Nrd1 [Experiment 2]

Project description:Here we report high-resolution analyses of transcribing RNAPIII in either a wild-type (WT) background or a Nrd1 auxin-inducible degron (AID) strain in which Nrd1 can be rapidly depleted upon addition of the auxin analogue Indole-3-acetic acid (IAA). Nrd1 functions together with Sen1 in transcription termination at RNAPII-dependent non-coding genes. Here we show that depletion of Nrd1 does not affect transcription termination at RNAPIII-dependent genes, indicating that Nrd1 is not an RNAPIII transcription termination factor.

2022-07-13 | GSE174699 | GEO

Comparative transcriptome analysis of basal gene expression in Wild-type and Sen1ΔN mutant of Saccharomyces cerevisiae

Project description:In Saccharomyces cerevisiae, Sen1 is a 252-kDa, nuclear superfamily-1 RNA/DNA helicase that encoded by an essential gene SEN1 (Senataxin). It is an important component of the Nrd1p-Nab3p-Sen1p (NRD1) complex that regulates the transcriptional termination of most non-coding and some coding transcripts at RNA polymerase pause sites. Sen1 specifically interacts with Rnt1p (RNase III), an endoribonuclease, and with Rpb1p (Rpo21p), a subunit of RNA polymerase II, through its N-terminal domain (NTD), which is a critical element of the RNA-processing machinery. Moreover, mutations in the N-terminal tail of SETX, a human ortholog of yeast Senataxin (Sen1) reported in neurological disorders. In one of the earlier studies, we have reported that the loss of dispensable NTD in yeast Sen1 resulted in flocculation and slow growing phenotypes along with defective DNA damage repair mechanisms. So, we attempted to explore the molecular basis of functional impairment associated with the loss of Sen1 N-terminal domain through global oligonucleotide microarray analysis. Also, we investigated for functionally enriched pathways based on the altered basal level gene expression profiles upon NTD loss of Sen1. The microarray data were validated by quantitative real-time PCR wherever necessary.

2016-10-12 | GSE75447 | GEO

The Sen1 Helicase Prevents Spurious Transcription by Controlling Genome-Wide Transcription Termination by RNAPII

2011-06-01 | GSE19015 | GEO

Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription

Project description:Yeast Sen1Senataxin is a RNA/DNA helicase that preserves replication forks across RNA Polymerase II-transcribed genes by counteracting RNA:DNA hybrids accumulation. We show that in Sen1-depleted cells early forks clashing head-on with transcription halt, and impair progression of sister forks within the same replicon. Unsolved replication-transcription collisions trigger the local firing of dormant origins that rescue arrested forks. In sen1 mutants the MRX and Mrc1/Ctf4-complexes protect those forks clashing with transcription by preventing genotoxic fork-resection events mediated by the Exo1 nuclease. Hence, sister forks within the same replicon remain coupled when one of the two forks halts. This is different when forks encounter double strand breaks. Moreover, the local firing of dormant origins is not prevented by checkpoint activation but depends on delayed adjacent forks. Furthermore, a productive head-on clash between replication and transcription requires the tuning of origin firing and coordination between Sen1, the MRX and Mrc1/Ctf4-complexes and Exo1.

2017-10-11 | GSE97046 | GEO

Saccharomyces cerevisiae

Project description:Senataxin associates with replication forks to protect fork integrity across RNAPII transcribed genes

| PRJNA170079 | ENA