Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1103704 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28779115_1.fastq.gz | Fastqsanger.gz | |||
| SRR28779115_2.fastq.gz | Fastqsanger.gz | |||
| SRR28779116_1.fastq.gz | Fastqsanger.gz | |||
| SRR28779116_2.fastq.gz | Fastqsanger.gz | |||
| SRR28779117_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
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Project description:The response to DNA damage-stalled RNA polymerase II (RNAPIIo) involves the assembly of the transcription-coupled repair (TCR) complex on actively transcribed strands. The function of the TCR proteins CSB, CSA and UVSSA and the manner in which the core DNA repair complex, including transcription factor IIH (TFIIH), is recruited are largely unknown. Here, we define the assembly mechanism of the TCR complex in human isogenic knockout cells. We show that TCR is initiated by RNAPIIobound CSB, which recruits CSA through a newly identified CSA-interaction motif (CIM). Once recruited, CSA facilitates the association of UVSSA with stalled RNAPIIo. Importantly, we find that UVSSA is the key factor that recruits the TFIIH complex in a manner that is stimulated by CSB and CSA. Together these findings reveal a sequential and highly cooperative assembly mechanism of TCR proteins and reveal the mechanism for TFIIH recruitment to DNA damage-stalled RNAPIIo to initiate repair.
2020-04-14 | PXD017329 | Pride
Project description:Removal of transcription-blocking DNA lesions requires the binding of transcription-coupled repair (TCR) factors to DNA damage-stalled RNA polymerase II (RNAPII). The full repertoire of factors required for TCR remains to be elucidated. Through genome-wide CRISPR screens and strand-specific ChIP-seq, we identify the RNAPII-associated factor ELOF1 as a new core TCR component. Mechanistically, ELOF1 does not affect the association of TCR components CSB and the CRL4CSA ubiquitin ligase, but instead regulates RNAPII ubiquitylation, and subsequent ubiquitin-dependent recruitment of repair factors. This function requires its constitutive interaction with RNAPII close to the K1268 site, revealing ELOF1 as a specificity factor that positions CRL4CSA for optimal RNAPII ubiquitylation to orchestrate transcription-coupled repair. Finally, ELOF1 operates in a second transcription stress-response pathway, regulated by the deubiquitylating enzyme OTUD5.
2021-04-20 | GSE149760 | GEO
Project description:The response to DNA damage-stalled RNA polymerase II (RNAPIIo) involves the assembly of the transcription-coupled repair (TCR) complex on actively transcribed strands. The function of the TCR proteins CSB, CSA and UVSSA and the manner in which the core DNA repair complex, including transcription factor IIH (TFIIH), is recruited is largely unknown. Here, we define the assembly mechanism of the TCR complex in human isogenic knockout cells. We show that TCR is initiated by RNAPIIo-bound CSB, which recruits CSA through a newly identified CSA-interaction domain (CID). Once recruited, CSA facilitates the association of UVSSA with stalled RNAPIIo. Importantly, we find that UVSSA is the key factor that regulates the assembly of the TFIIH complex in a manner that is stabilized by CSB and CSA. We identify the UV-specific and independent interactors of UVSSA
2020-04-14 | PXD013572 | Pride
Project description:Transcription-coupled DNA repair is widespread in nature having been found in organisms from E. coli to yeast to humans. In E. coli, the transcription-repair coupling factor (TRCF) encoded by the mfd gene recognizes RNA polymerase (RNAP) stalled at a damage site and recruits the excision repair proteins to the stalled RNAP and promotes damage recognition while displacing RNAP and the truncated transcript from the damage site and in doing so, enhances the rate of repair of the transcribed strand (TS). Recently, it has been reported that there are other E. coli proteins that mediate transcription-coupled repair (TCR) independently of the Mfd protein. To understand the relative contributions of various proteins to and mechanisms of TCR we used the recently developed nucleotide excision repair sequencing (XR-seq) method for genome-wide analysis of excision repair to generate excision repair maps of entire genomes of various E. coli strains with deletions of genes implicated in TCR. Our data show that the Mfd protein catalyzes TCR throughout the genome.
2017-02-08 | GSE92734 | GEO
Project description:Correct transcription is crucial for life. However, DNA damage severely impedes elongating RNA Polymerase II (Pol II), causing transcription inhibition and transcription-replication conflicts. Cells are equipped with intricate mechanisms to counteract the severe consequence of these transcription-blocking lesions (TBLs). However, the exact mechanism and factors involved remain largely unknown. Here, using a genome-wide CRISPR/cas9 screen, we identified elongation factor ELOF1 as an important new factor in the transcription stress response upon DNA damage. We show that ELOF1 has an evolutionary conserved role in Transcription-Coupled Nucleotide Excision Repair (TC-NER), where it promotes recruitment of the TC-NER factors UVSSA and TFIIH to efficiently repair TBLs and resume transcription. Additionally, ELOF1 modulates transcription to protect cells from transcription-mediated replication stress, thereby preserving genome stability. Thus, ELOF1 protects the transcription machinery from DNA damage via two distinct mechanisms.
2021-04-20 | PXD025304 | Pride
Project description:In adaptive immunity, transcription-coupled damage is introduced into antibody genes by activation-induced cytidine deaminase (AID) to diversify antibody repertoire. However, the coordination between transcription and DNA damage/repair remains elusive. Here, we find that transcription elongation factor 1 (ELOF1) stabilizes paused RNA polymerase II (RNAPII) at transcription barriers, providing a platform for transcription-coupled DNA damage/repair. Using a genetic screen, we discover that ELOF1 is required for AID targeting and that ELOF1 deficiency results in defective antibody class switch recombination and somatic hypermutation in mice. While downstream transcription-coupled repair factors are dispensable for AID-damage, ELOF1 mechanistically facilitates both transcription-coupled damage and repair by stabilizing chromatin-bound RNAPII. In ELOF1-deficient cells, paused RNAPII tends to detach from chromatin and fails to recruit factors to induce or repair DNA damage. Our study places ELOF1 at the center of transcription-coupled DNA metabolism processes and suggests a transition of RNAPII from elongation to a DNA damage/repair scaffold.
2025-03-01 | GSE284305 | GEO
Project description:In adaptive immunity, transcription-coupled damage is introduced into antibody genes by activation-induced cytidine deaminase (AID) to diversify antibody repertoire. However, the coordination between transcription and DNA damage/repair remains elusive. Here, we find that transcription elongation factor 1 (ELOF1) stabilizes paused RNA polymerase II (RNAPII) at transcription barriers, providing a platform for transcription-coupled DNA damage/repair. Using a genetic screen, we discover that ELOF1 is required for AID targeting and that ELOF1 deficiency results in defective antibody class switch recombination and somatic hypermutation in mice. While downstream transcription-coupled repair factors are dispensable for AID-damage, ELOF1 mechanistically facilitates both transcription-coupled damage and repair by stabilizing chromatin-bound RNAPII. In ELOF1-deficient cells, paused RNAPII tends to detach from chromatin and fails to recruit factors to induce or repair DNA damage. Our study places ELOF1 at the center of transcription-coupled DNA metabolism processes and suggests a transition of RNAPII from elongation to a DNA damage/repair scaffold.
2025-03-01 | GSE284306 | GEO
Project description:In adaptive immunity, transcription-coupled damage is introduced into antibody genes by activation-induced cytidine deaminase (AID) to diversify antibody repertoire. However, the coordination between transcription and DNA damage/repair remains elusive. Here, we find that transcription elongation factor 1 (ELOF1) stabilizes paused RNA polymerase II (RNAPII) at transcription barriers, providing a platform for transcription-coupled DNA damage/repair. Using a genetic screen, we discover that ELOF1 is required for AID targeting and that ELOF1 deficiency results in defective antibody class switch recombination and somatic hypermutation in mice. While downstream transcription-coupled repair factors are dispensable for AID-damage, ELOF1 mechanistically facilitates both transcription-coupled damage and repair by stabilizing chromatin-bound RNAPII. In ELOF1-deficient cells, paused RNAPII tends to detach from chromatin and fails to recruit factors to induce or repair DNA damage. Our study places ELOF1 at the center of transcription-coupled DNA metabolism processes and suggests a transition of RNAPII from elongation to a DNA damage/repair scaffold.
2025-03-01 | GSE284303 | GEO
Project description:The precise regulation of RNA Polymerase II (Pol II) transcription after genotoxic stress is crucial for proper execution of the DNA damage-induced stress response. While stalling of Pol II on transcription-blocking lesions (TBLs) blocks transcript elongation and initiates DNA repair in cis, TBLs additionally elicit a response in trans that regulates transcription genome-wide. Here we uncover that after an initial elongation block in cis, TBLs trigger the genome-wide VCP-mediated proteasomal degradation of promoter-paused Pol II in trans. This degradation is mechanistically distinct from processing of TBL-stalled Pol II, is signaled via GSK3, and contributes to the TBL-induced transcription block, even in transcription-coupled repair-deficient cells. Thus, our data reveal the targeted degradation of promoter-bound Pol II as an important new component of the transcription stress response that enables the genome-wide adaptation of transcription to genotoxic stress.
2022-06-27 | GSE169480 | GEO