Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1056281 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27335082.fastq.gz | Fastqsanger.gz | |||
| SRR27335083.fastq.gz | Fastqsanger.gz | |||
| SRR27335084.fastq.gz | Fastqsanger.gz | |||
| SRR27335085.fastq.gz | Fastqsanger.gz | |||
| SRR27335086.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 14 |
Similar Datasets
Project description:Collisions of the transcription and replication machineries on the same DNA strand can pose a significant threat to genomic stability. These collisions occur in part due to the formation of RNA-DNA hybrids termed R-loops, in which a newly transcribed RNA molecule hybridizes with the DNA template strand. This study investigated the role of RAD52, a known DNA repair factor, in preventing collisions by directing R-loop formation and resolution. We show that RAD52 deficiency increases R-loop accumulation, exacerbating collisions and resulting in elevated DNA damage. Furthermore, RAD52's ability to interact with the transcription machinery, coupled with its capacity to facilitate R-loop dissolution, highlights its role in preventing collisions. Lastly, we provide evidence of an increased mutational burden from double-strand breaks at conserved R-loop sites in human tumor samples, which is increased in tumors with low RAD52 expression. In summary, this study underscores the importance of RAD52 in orchestrating the balance between replication and transcription processes to prevent collisions and maintain genome stability.
2024-08-25 | PXD054611 | Pride
Project description:Collisions of transcription and replication machinery on the same DNA strand can pose a significant threat to genomic stability. These collision occur in part due to of RNA-DNA hybrids termed R-loops, in which a newly synthesized RNA molecule hybridizes with the DNA template strand. This study investigated the novel role of RAD52, a known DNA repair factor, in preventing collisions by managing R-loop formation and resolution. We show that RAD52 deficiency increases R-loop accumulation, exacerbating collisions and resulting in elevated DNA damage. Further, RAD52's ability to interact with the transcription machinery, coupled with its capacity to facilitate R-loop dissolution, highlights its role in preventing collisions. Lastly, we provide the first evidence of an increased mutational burden at conserved R-loop sites in human tumor samples. In summary, this study underscores the importance of RAD52 in orchestrating the delicate balance between replication and transcription processes to prevent collisions and maintain genome stability.
2024-07-11 | GSE266483 | GEO
Project description:R loops are an important source of genome instability largely due to its negative impact on replication progression. Yra1/ALY is an abundant RNA-binding factor conserved from yeast to humans and required for mRNA export, but its excess cause lethality and genome instability. Here, we show that Yra1 binds RNA-DNA hybrids in vitro and when artificially overexpressed is recruited to chromatin in an RNA-DNA hybrid-dependent manner stabilizing R loops and converting them into replication obstacles in vivo. Importantly, excess of Yra1 increases R loop-mediated genome instability caused by transcription-replication collisions regardless of whether they are co-directional or head-on. It also induces telomere shortening and senescence, consistent with a defect in telomere replication. Our results indicate that R loops form transiently in cells regardless of replication and, after stabilization by excess Yra1, they compromise genome integrity, in agreement with a two-step model of R loop-mediated genome instability. This work opens new perspectives to understand transcription-associated genome instability in repair-deficient cells, including tumoral cells.
2018-06-27 | GSE113580 | GEO
Project description:Transcription is a major obstacle for replication fork progression and transcription-replication collisions constitute a main cause of genome instability. At a genome-wide scale these obstacles can be detected by the accumulation of the replicative Rrm3 helicase required for RF progression through protein obstacles. Here we show that FACT, a chromatin-reorganizing complex that swaps nucleosomes around the RNA polymerase during transcription elongation and that also has a role in replication, is needed to resolve transcription-replication conflicts in Saccharomyces cerevisiae. Importantly, ChIP-chip analyses of Rrm3 reveal that replication progression impairment in FACT mutants occur genome-wide, but preferentially at highly transcribed regions. ChIP-chip studies were perfomed with antibodies against Rrm3-FLAG in the yeast S. cerevisiae.
2014-03-17 | E-GEOD-51653 | biostudies-arrayexpress
Project description:Head-on collisions between the DNA replication machinery and RNA polymerase are potent genotoxic events leading to replication fork stalling, R-loop formation, and DNA breaks. Current models suggest that head-on collisions are avoided through replication initiation site (RIS) placement upstream of active genes, thus ensuring co-orientation of replication fork movement and genic transcription. However, this model does not account for pervasive transcription units, or intragenic replication initiation events. Through mining phased GRO-seq data, and developing a rigorous informatic strategy to identify RIS, we demonstrate that head-on transcription occurs frequently in a breast cancer cell line, and that this transcription is significantly downregulated during S-phase, particularly in regions susceptible to R-loop formation. Collectively, our analysis suggests the existence of a temporally tuned transcriptional regulation mechanism that functions to maintain genome stability.
2022-04-30 | GSE201746 | GEO
Project description:Cisplatin treatment causes genome instability by single-strand annealing (SSA) activation in some cancer cells. Therefore, we checked whether EGC, a RAD52 inhibitor, can restrain genome instability induced by cisplatin treatment.
2019-09-09 | GSE113384 | GEO
Project description:Breast cancer linked with BRCA1/2 mutations commonly recur and resist current therapies, including PARP inhibitors. Given the lack of effective targeted therapies for BRCA1-mutant cancers, we sought to identify novel targets to selectively kill these cancers. Here, we report that loss of RNF8 significantly protects Brca1-mutant mice against mammary tumorigenesis. RNF8 deficiency in human BRCA1-mutant breast cancer cells was found to promote R-loop accumulation and replication fork instability, leading to increased DNA damage, senescence, and synthetic lethality. Mechanistically, RNF8 interacts with XRN2, which is crucial for transcription termination and R-loop resolution. We report that RNF8 ubiquitylates XRN2 to facilitate its recruitment to R-loop-prone genomic loci and that RNF8 deficiency in BRCA1-mutant breast cancer cells decreases XRN2 occupancy at R-loop-prone sites, thereby promoting R-loop accumulation, transcription-replication collisions, excessive genomic instability, and cancer cell death. Collectively, our work identifies a synthetic lethal interaction between RNF8 and BRCA1, which is mediated by a pathological accumulation of R-loops.
2023-09-14 | GSE202723 | GEO
Project description:Transcription is a major obstacle for replication fork progression and transcription-replication collisions constitute a main cause of genome instability. At a genome-wide scale these obstacles can be detected by the accumulation of the replicative Rrm3 helicase required for RF progression through protein obstacles. Here we show that FACT, a chromatin-reorganizing complex that swaps nucleosomes around the RNA polymerase during transcription elongation and that also has a role in replication, is needed to resolve transcription-replication conflicts in Saccharomyces cerevisiae. Importantly, ChIP-chip analyses of Rrm3 reveal that replication progression impairment in FACT mutants occur genome-wide, but preferentially at highly transcribed regions.
2014-03-17 | GSE51653 | GEO
Project description:Non-scheduled R loops represent a major source of DNA damage and replication stress. Cells have different ways to prevent R loop accumulation. One mechanism relies on the conserved THO complex in association with co-transcriptional RNA processing factors including the RNA-dependent ATPase UAP56/DDX39B and histone modifiers such as the SIN3 deacetylase in humans. We investigated the function of UAP56/DDX39B in R loop removal. We show that UAP56 depletion causes R loop accumulation, R loop-mediated genome instability and replication fork stalling. We demonstrate an RNA-DNA helicase activity in UAP56 and that its overexpression suppresses R loops and genome instability induced by depleting 5 different unrelated factors. UAP56/DDX39B localizes to active chromatin and prevents the accumulation of RNA-DNA hybrids over the entire genome. We propose that, in addition to its RNA processing role, UAP56/DDX39B is a key helicase required to eliminate harmful co-transcriptional RNA structures that otherwise would block transcription and replication.
2020-05-25 | GSE127979 | GEO