ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Pre-rRNA Facilitates TopBP1-Mediated DNA Double-Strand Break Response.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The trial behind it
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- BARD1 recognizes pre-rRNA for DNA damage repair and rRNA biogenesis.The Journal of biological chemistry · 2026Article
- tRNA-derived fragment tRF-24 drives CELF1 phase separation to promote oncogenic splicing in esophageal squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Pre-rRNAs control mitosis by maintaining chromosomal segregation through protecting SMC2 from AURKA-mediated phosphorylation.Cell death & disease · 2025Article
- Unveiling the dynamic drivers: phase separation's pivotal role in stem cell biology and therapeutic potential.Stem cell research & therapy · 2025Review
- Pre-rRNA Facilitates TopBP1-Mediated DNA Double-Strand Break Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
In response to genotoxic stress-induced DNA damage, TopBP1 mediates ATR activation for signaling transduction and DNA damage repair. However, the detailed molecular mechanism remains elusive. Here, using unbiased protein affinity purification and RNA sequencing, it is found that TopBP1 is associated with pre-ribosomal RNA (pre-rRNA). Pre-rRNA co-localized with TopBP1 at DNA double-strand breaks (DSBs). Similar to pre-rRNA, ribosomal proteins also colocalize with TopBP1 at DSBs. The recruitment of TopBP1 to DSBs is suppressed when cells are transiently treated with RNA polymerase I inhibitor (Pol I-i) to suppress pre-rRNA biogenesis but not protein translation. Moreover, the BRCT4-5 of TopBP1 recognizes pre-rRNA and forms liquid-liquid phase separation (LLPS) with pre-rRNA, which may be the molecular basis of DSB-induced foci of TopBP1. Finally, Pol I-i treatment impairs TopBP1-associated cell cycle checkpoint activation and homologous recombination repair. Collectively, this study reveals that pre-rRNA plays a key role in the TopBP1-dependent DNA damage response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.