Genome-wide homeostatic regulation of R-loops by the dual RNA-DNA topoisomerase, topoisomerase III-β (TOP3B) I
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1199475 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome-wide homeostatic regulation of R-loops by the dual RNA-DNA topoisomerase, topoisomerase III-β (TOP3B) III
| PRJNA1199490 | ENA
Project description:Genome-wide homeostatic regulation of R-loops by the dual RNA-DNA topoisomerase, topoisomerase III-β (TOP3B) II
| PRJNA1199483 | ENA
Project description:We report the mapping of R-loops across the human genome in wild-type and TOP3B-KO HCT116 and HT1080 cells by performing DNA: RNA Immunoprecipitation followed by high-throughput sequencing (DRIP-seq). Cellular depletion of TOP3B globally increases the intensity of pre-existing R-loops. The enriched R-loop peaks in TOP3B-KO cells are both in intergenic and genic regions, including protein-coding and non-coding RNA genes. Long genes and genes with high exon-intron junctions accumulate more R-loops. Global transcription analyses indicate that increased R-loop signals do not significantly change transcript level in TOP3B-KO cells. However, increased R-loops in TOP3B-KO cells cause stabilization of G4-quadruplexs and increased gH2AX foci. Altogether, these results demonstrate that TOP3B is needed for the removal of deleterious R-loops that lead to genomic breaks.
2025-09-04 | GSE284536 | GEO
Project description:We report the mapping of R-loops across the human genome in wild-type and TOP3B-KO HCT116 and HT1080 cells by performing DNA: RNA Immunoprecipitation followed by high-throughput sequencing (DRIP-seq). Cellular depletion of TOP3B globally increases the intensity of pre-existing R-loops. The enriched R-loop peaks in TOP3B-KO cells are both in intergenic and genic regions, including protein-coding and non-coding RNA genes. Long genes and genes with high exon-intron junctions accumulate more R-loops. Global transcription analyses indicate that increased R-loop signals do not significantly change transcript level in TOP3B-KO cells. However, increased R-loops in TOP3B-KO cells cause stabilization of G4-quadruplexs and increased gH2AX foci. Altogether, these results demonstrate that TOP3B is needed for the removal of deleterious R-loops that lead to genomic breaks.
2025-09-04 | GSE284535 | GEO
Project description:We report the mapping of R-loops across the human genome in wild-type and TOP3B-KO HCT116 and HT1080 cells by performing DNA: RNA Immunoprecipitation followed by high-throughput sequencing (DRIP-seq). Cellular depletion of TOP3B globally increases the intensity of pre-existing R-loops. The enriched R-loop peaks in TOP3B-KO cells are both in intergenic and genic regions, including protein-coding and non-coding RNA genes. Long genes and genes with high exon-intron junctions accumulate more R-loops. Global transcription analyses indicate that increased R-loop signals do not significantly change transcript level in TOP3B-KO cells. However, increased R-loops in TOP3B-KO cells cause stabilization of G4-quadruplexs and increased gH2AX foci. Altogether, these results demonstrate that TOP3B is needed for the removal of deleterious R-loops that lead to genomic breaks.
2025-09-04 | GSE284530 | GEO
Project description:DNA double-stranded breaks (DSBs) pose a significant threat to genomic integrity, and their generation during essential cellular processes like transcription remains poorly understood. In this study, we employed advanced techniques to map DSBs, R-loops, and Topoisomerase 1 cleavage complex (TOP1cc) and re-analyzed ChIP-seq and DRIP-seq data to comprehensively investigate the interplay between transcription, DSBs, Topoisomerase 1 (TOP1), and R-loops. Our findings revealed the presence of DSBs at highly expressed genes enriched with TOP1 and R-loops, indicating their crucial involvement in transcription-associated genomic instability. Depletion of R-loops and TOP1 specifically reduced DSBs at highly expressed genes, uncovering their pivotal roles in transcriptional DSB formation. By elucidating the intricate interplay between TOP1cc trapping, R-loops, and DSBs, our study provides novel insights into the mechanisms underlying transcription-associated genomic instability. Moreover, we establish a link between transcriptional DSBs and early molecular changes driving cancer development. Notably, our study highlights the distinct etiology and molecular characteristics of driver mutations compared to passenger mutations, shedding light on the potential for targeted therapeutic strategies. Overall, these findings deepen our understanding of the regulatory mechanisms governing DSBs in hypertranscribed genes associated with carcinogenesis, opening avenues for future research and therapeutic interventions. This SuperSeries is composed of the SubSeries listed below.
2024-05-22 | GSE241309 | GEO
Project description:Topoisomerase 3β (TOP3B) and TDRD3 form a dual-activity topoisomerase complex that interacts with FMRP and can change the topology of both DNA and RNA. Here, we investigated the post-transcriptional influence of TOP3B and associated proteins on mRNA translation and turnover. First, we discovered that in human HCT116 colon cancer cells, knock-out (KO) of TOP3B had similar effects on mRNA turnover and translation as did TDRD3-KO, while FMRP-KO resulted in rather distinct effects, indicating that TOP3B had stronger coordination with TDRD3 than FMRP in mRNA regulation. Second, we identified TOP3B-bound mRNAs in HCT116 cells; we found that while TOP3B did not directly influence the stability or translation of most TOP3B target mRNAs, it stabilized a subset of target mRNAs but had a more complex effect on translation--enhancing for some mRNAs whereas reducing for others. Interestingly, a point mutation that specifically disrupted TOP3B catalytic activity only partially recapitulated the effects of TOP3B-KO on mRNA stability and translation, suggesting that the impact of TOP3B on target mRNAs is only in part linked to its ability to change topology of mRNAs. Collectively, our data suggest that TOP3B-TDRD3 can regulate mRNA translation and turnover by mechanisms that are dependent and independent of topoisomerase activity.
2022-06-08 | GSE188574 | GEO
Project description:A dual-activity topoisomerase complex regulates mRNA translation and turnover
| PRJNA779461 | ENA
Project description:Topoisomerase III-beta (Top3b) reduces nucleic acid torsional stress and intertwining generated during RNA and DNA metabolism while protecting the genome from pathological R-loops, which otherwise result in DNA breakage and genome instability. By studying Top3b knockout mice (Top3b-KO), we find that the loss of Top3b accelerates the development of spontaneous atypical lymphoid hyperplasia and lymphomas arising in spleens and lymph nodes, the organs with prominent Top3b expression. Aging Top3b-KO mice also display splenomegaly and systemic immune alterations including neutrophilia and lymphopenia consistent with chronic inflammation. At the molecular level, Top3b deficiency causes genome-wide R-loop accumulation in splenocytes as measured by CUT&Tag sequencing. Increased R-loops are associated with genomic breaks and activation of immune signaling pathways including innate and adaptive immune cell signaling, IL-4 signaling, FAK signaling and cGAS-STING. Additionally, knocking-out Top3b promotes the rapid development of syngeneic EL4 T-cell lymphomas. In conclusion, our work suggests that Top3b protects from lymphoma, tumorigenesis and immune dysregulations.
2025-09-05 | GSE293641 | GEO
Project description:Topoisomerase III-beta (Top3b) reduces nucleic acid torsional stress and intertwining generated during RNA and DNA metabolism while protecting the genome from pathological R-loops, which otherwise result in DNA breakage and genome instability. By studying Top3b knockout mice (Top3b-KO), we find that the loss of Top3b accelerates the development of spontaneous atypical lymphoid hyperplasia and lymphomas arising in spleens and lymph nodes, the organs with prominent Top3b expression. Aging Top3b-KO mice also display splenomegaly and systemic immune alterations including neutrophilia and lymphopenia consistent with chronic inflammation. At the molecular level, Top3b deficiency causes genome-wide R-loop accumulation in splenocytes as measured by CUT&Tag sequencing. Increased R-loops are associated with genomic breaks and activation of immune signaling pathways including innate and adaptive immune cell signaling, IL-4 signaling, FAK signaling and cGAS-STING. Additionally, knocking-out Top3b promotes the rapid development of syngeneic EL4 T-cell lymphomas. In conclusion, our work suggests that Top3b protects from lymphoma, tumorigenesis and immune dysregulations.
2025-09-05 | GSE293640 | GEO