Regulation of the RNAPII Pool Is Integral to the DNA Damage Response [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA600922 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10877200_1.fastq.gz | Fastqsanger.gz | |||
| SRR10877200_2.fastq.gz | Fastqsanger.gz | |||
| SRR10877201_1.fastq.gz | Fastqsanger.gz | |||
| SRR10877201_2.fastq.gz | Fastqsanger.gz | |||
| SRR10877202_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:In response to transcription-blocking DNA damage, cells orchestrate a multi-pronged reaction, involving transcription-coupled DNA repair, degradation of RNAPII and genome-wide transcription shutdown. How these responses are connected has remained unclear. Here we show that damage-induced ubiquitylation of RNAPII itself, at a single lysine (RPB1 K1268), is the focal point for DNA damage response coordination. K1268-ubiquitylation affects DNA repair and signals RNAPII degradation, essential for surviving genotoxic insult. It is also crucial for transcriptional shutdown, in the absence of which cells display dramatic transcriptome alterations. Additionally, regulation of RNAPII stability is central to transcription recovery – indeed, depletion of the RNAPII pool underlies the failure of this process in Cockayne syndrome B cells. These data expose regulation of global RNAPII levels as integral to the cellular DNA damage response, and open the intriguing possibility that RNAPII pool size generally affects cell-specific transcription programmes, in genome instability disorders and even normal cells.
2020-01-14 | GSE143518 | GEO
Project description:In response to transcription-blocking DNA damage, cells orchestrate a multi-pronged reaction, involving transcription-coupled DNA repair, degradation of RNAPII and genome-wide transcription shutdown. How these responses are connected has remained unclear. Here we show that damage-induced ubiquitylation of RNAPII itself, at a single lysine (RPB1 K1268), is the focal point for DNA damage response coordination. K1268-ubiquitylation affects DNA repair and signals RNAPII degradation, essential for surviving genotoxic insult. It is also crucial for transcriptional shutdown, in the absence of which cells display dramatic transcriptome alterations. Additionally, regulation of RNAPII stability is central to transcription recovery – indeed, depletion of the RNAPII pool underlies the failure of this process in Cockayne syndrome B cells. These data expose regulation of global RNAPII levels as integral to the cellular DNA damage response, and open the intriguing possibility that RNAPII pool size generally affects cell-specific transcription programmes, in genome instability disorders and even normal cells.
2020-01-14 | GSE143537 | GEO
Project description:In response to transcription-blocking DNA damage, cells orchestrate a multi-pronged reaction, involving transcription-coupled DNA repair, degradation of RNAPII and genome-wide transcription shutdown. How these responses are connected has remained unclear. Here we show that damage-induced ubiquitylation of RNAPII itself, at a single lysine (RPB1 K1268), is the focal point for DNA damage response coordination. K1268-ubiquitylation affects DNA repair and signals RNAPII degradation, essential for surviving genotoxic insult. It is also crucial for transcriptional shutdown, in the absence of which cells display dramatic transcriptome alterations. Additionally, regulation of RNAPII stability is central to transcription recovery – indeed, depletion of the RNAPII pool underlies the failure of this process in Cockayne syndrome B cells. These data expose regulation of global RNAPII levels as integral to the cellular DNA damage response, and open the intriguing possibility that RNAPII pool size generally affects cell-specific transcription programmes, in genome instability disorders and even normal cells.
2020-01-14 | GSE143529 | GEO
Project description:Regulation of the RNAPII Pool Is Integral to the DNA Damage Response
| PRJNA600921 | ENA
Project description:Regulation of the RNAPII Pool Is Integral to the DNA Damage Response [TT-seq]
| PRJNA600880 | ENA
Project description:Regulation of the RNAPII Pool Is Integral to the DNA Damage Response [TT-seq CSBKO]
| PRJNA600884 | ENA
Project description:In response to transcription-blocking DNA damage, cells orchestrate a multi-pronged reaction, involving transcription-coupled DNA repair, degradation of RNA polymerase II (RNAPII), and genome-wide transcription shutdown. Here, we provide insight into how these responses are connected by the finding that ubiquitylation of RNAPII itself, at a single lysine (RPB1 K1268), is the focal point for DNA-damage-response coordination. K1268 ubiquitylation affects DNA repair and signals RNAPII degradation, essential for surviving genotoxic insult. RNAPII degradation results in a shutdown of transcriptional initiation, in the absence of which cells display dramatic transcriptome alterations. Additionally, regulation of RNAPII stability is central to transcription recovery-persistent RNAPII depletion underlies the failure of this process in Cockayne syndrome B cells. These data expose regulation of global RNAPII levels as integral to the cellular DNA-damage response and open the intriguing possibility that RNAPII pool size generally affects cell-specific transcription programs in genome instability disorders and even normal cells.
| S-EPMC7103762 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-01-14 | GSE143542 | GEO
Project description:Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII promotes activation of the ATM kinase at TRCs to drive DNA repair. We show the ATPase Wrnip1 that binds and protects stalled replication forks, associates with RNAPII and limits ATM activation. Wrnip1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase Huwe1. Mutation of Huwe1 promotes the transfer of Wrnip1 onto replisome and induces TRCs stimulating ATM activation on RNAPII. This mechanism is evoked early upon replicative stress to induce Wrnip1 translocation and ATM signaling at TRCs. Thus, although primarily considered as genotoxic events, TRCs can provide a mechanism to maintain genome stability under replicative stress.
2023-07-31 | PXD037680 | Pride
Project description:Cancer cells develop strong genetic dependencies enabling survival under oncogenic stress. MYC is a key oncogene activated across most cancers, and identifying associated synthetic lethality can provide important clues about its activity and potential therapeutic strategies. Based on previously conducted genome-wide screenings we identified UVSSA, a gene involved in transcription-coupled repair whose knockdown decreased cell viability when combined with MYC activation. Synthetic lethal interactions between MYC expression and UVSSA loss correlated with ATM/CHK2 activation, suggesting increased genome instability. We show that although the synthetic lethal interaction was diminished by attenuating RNA polymerase II (RNAPII) activity, it becomes independent of UV-induced damage repair, suggesting that UVSSA has a critical function in regulating transcription in the absence of exogenous DNA damage. Supporting this hypothesis, RNAPII-ChIP-seq revealed that MYC-dependent increase in RNAPII promoter occupancy, as well as RNAPII stalling, is reduced or abrogated by UVSSA knockdown, suggesting that UVSSA negatively regulates MYC-dependent transcription. Taken together, our data shows that the UVSSA complex is required to limit MYC-dependent transcription stress and to maintain cell survival. While the role of UVSSA in regulating RNAPII dynamics has only been documented thus far in the context of UV-induced DNA damage repair, we propose that its activity is also required to cope with transcription stress induced by oncogene activation.
2020-10-28 | GSE121960 | GEO