ArticleNature communications2024
Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Polymerase face-off: emerging concepts in transcription-replication coordination.EMBO reports · 2026Review
- Dynamic regulation of origin firing factors links CDK activity to dormant origin activation.Nature communications · 2026Article
- NELF prevents transcriptional readthrough into DNA replication zones in cancer cells.EMBO reports · 2026Article
- Transcription termination counteracts DNA damage after WEE1 inhibition.Nucleic acids research · 2026Article
- Ensemble Machine Learning on Bulk RNA-Seq Identifies 17-Gene Signature Predicting Neoadjuvant Chemotherapy Response in Breast Cancer.Current issues in molecular biology · 2026Article
- OCT4 enhances the firing efficiency of late DNA replication origins in mouse embryonic stem cells.Nature communications · 2026Article
- Emerging roles of RNA:DNA hybrid regulation by mammalian ribonuclease H2 in replication stress and cancer.Journal of cell science · 2025Review
- Human RNase H2 upregulation counteracts oncogene- and chemotherapy-induced replication stress.Oncogene · 2025Article
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
- ZC3H4 safeguards genome integrity by preventing transcription-replication conflicts at noncoding RNA loci.Science advances · 2025Article
- Dynamic regulation of origin firing factors links CDK activity to dormant origin activation.bioRxiv : the preprint server for biology · 2025Article
- Selective interactions at pre-replication complexes categorize baseline and dormant origins.Nature communications · 2025Article
- Article
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Authors and funding
13 authors.
Funding
Abstract
BRCA2 is a tumor suppressor protein responsible for safeguarding the cellular genome from replication stress and genotoxicity, but the specific mechanism(s) by which this is achieved to prevent early oncogenesis remains unclear. Here, we provide evidence that BRCA2 acts as a critical suppressor of head-on transcription-replication conflicts (HO-TRCs). Using Okazaki-fragment sequencing (Ok-seq) and computational analysis, we identified origins (dormant origins) that are activated near the transcription termination sites (TTS) of highly expressed, long genes in response to replication stress. Dormant origins are a source for HO-TRCs, and drug treatments that inhibit dormant origin firing led to a reduction in HO-TRCs, R-loop formation, and DNA damage. Using super-resolution microscopy, we showed that HO-TRC events track with elongating RNA polymerase II, but not with transcription initiation. Importantly, RNase H2 is recruited to sites of HO-TRCs in a BRCA2-dependent manner to help alleviate toxic R-loops associated with HO-TRCs. Collectively, our results provide a mechanistic basis for how BRCA2 shields against genomic instability by preventing HO-TRCs through both direct and indirect means occurring at predetermined genomic sites based on the pre-cancer transcriptome.
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