Sen1 and Rrm3 ensure permissive topological conditions for replication termination [ChIP-chip]
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ABSTRACT:
PROVIDER: PRJNA887726 | ENA |
REPOSITORIES: ENA
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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 | GSE214908 | GEO
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
Project description:Sen1 and Rrm3 ensure permissive topological conditions for replication termination [ChIP-seq]
| PRJNA887754 | ENA
Project description:Sen1 and Rrm3 ensure permissive topological conditions for replication termination
| PRJNA887757 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-10-11 | GSE214930 | GEO
Project description:Functional engagement of RNA polymerase II (Pol II) with eukaryotic chromosomes is a fundamental and highly regulated biological process. Here we present the first high-resolution map of Pol II occupancy across the entire yeast genome. We compared a wild-type strain with a strain bearing a substitution in the Sen1 helicase, which is a Pol II termination factor for non-coding RNA genes. The wildtype pattern of Pol II distribution provides unexpected insights into the mechanisms by which genes are repressed or silenced. Remarkably, a single amino acid substitution that compromises Sen1 function causes profound changes in Pol II distribution over both non-coding and protein-coding genes, establishing an important function of Sen1 in the regulation of transcription. Given the strong similarity of the yeast and human Sen1 proteins, our results suggest that progressive neurological disorders caused by substitutions in the human Sen1 homolog, Senataxin, may be due to misregulation of transcription. Keywords: transcription termination, attenuation, silencing, non-coding RNA, Pol II, ChIP-chip
2006-12-11 | GSE6293 | GEO
Project description:Transcription profiling of yeast SEN1 mutant versus wild-type
2010-11-27 | E-TABM-863 | biostudies-arrayexpress
Project description:Pervasive transcription is a widespread phenomenon leading to the production of a plethora of non-coding RNAs (ncRNAs) without apparent function. Pervasive transcription poses a risk that needs to be controlled to prevent the perturbation of gene expression. In yeast, the highly conserved helicase Sen1 restricts pervasive transcription by inducing termination of non-coding transcription. However, the mechanisms underlying the specific function of Sen1 at ncRNAs are poorly understood. Here we identify a motif in an intrinsically disordered region of Sen1 that mimics the phosphorylated carboxy terminal domain (CTD) of RNA polymerase II and characterize structurally its recognition by the CTD-interacting domain of Nrd1, an RNA-binding protein that binds specific sequences in ncRNAs. In addition, we show that Sen1-dependent termination strictly requires the recognition of the Ser5-phosphorylated form of the CTD by the N-terminal domain of Sen1. Furthermore, we find that the N-terminal and the C-terminal domains of Sen1 can mediate intra-molecular interactions. Our results shed light onto the network of protein-protein interactions that control termination of non-coding transcription by Sen1.
2020-01-31 | GSE138465 | GEO
Project description:Here we report high-resolution analyses of transcribing RNAPIII in either a wild-type (WT) background , a sen1-3 mutant or a Sen1 auxin-inducible degron (AID) strain in which Sen1 can be rapidly depleted upon addition of the auxin analogue Indole-3-acetic acid (IAA). Sen1 is a well-characterized transcription termination factor for RNAPII-dependent genes in budding yeast. Here we show that the presence of three point mutations in sen1-3 that abrogate the interaction of Sen1 with RNAPIII, as well as the depletion of Sen1 provoke global transcription termination defects at RNAPIII-dependent genes. These results indicate that Sen1 is also a transcription termination factor for RNAPIII transcription units.
2022-07-13 | GSE174698 | GEO
Project description:Pervasive transcription is a widespread phenomenon leading to the production of a plethora of non-coding RNAs (ncRNAs) without apparent function. Pervasive transcription poses a risk that needs to be controlled to prevent the perturbation of gene expression. In yeast, the highly conserved helicase Sen1 restricts pervasive transcription by inducing termination of non-coding transcription. However, the mechanisms underlying the specific function of Sen1 at ncRNAs are poorly understood. Here we identify a motif in an intrinsically disordered region of Sen1 that mimics the phosphorylated carboxy terminal domain (CTD) of RNA polymerase II and characterize structurally its recognition by the CTD-interacting domain of Nrd1, an RNA-binding protein that binds specific sequences in ncRNAs. In addition, we show that Sen1-dependent termination strictly requires the recognition of the Ser5-phosphorylated form of the CTD by the N-terminal domain of Sen1. Furthermore, we find that the N-terminal and the C-terminal domains of Sen1 can mediate intra-molecular interactions. Our results shed light onto the network of protein-protein interactions that control termination of non-coding transcription by Sen1.
2020-01-31 | GSE138448 | GEO