ArticleProceedings of the National Academy of Sciences of the United States of America2023
The RPA-RNF20-SNF2H cascade promotes proper chromosome segregation and homologous recombination repair.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 22 citations in OpenAlex.
- Interdependent roles of BRCA1, CtBP, estrogen, and NADH/NAD+ ratio in error-prone repair, breast cancer initiation, and metastasis.Molecular biology reports · 2026Review
- A cell cycle-dependent transition of acetylation to phosphorylation regulates timely centrosome maturation.Nature communications · 2026Article
- RNF20 dynamically regulates RIG-I and MDA5 transcription and degradation via nucleocytoplasmic translocation to balance antiviral signaling.PLoS pathogens · 2026Article
- Structural insights into the Bre1-Lge1 and RNF20/RNF40-WAC interactions critical for H2B ubiquitination.Nucleic acids research · 2026Article
- RNF216 as a Promising Biomarker for Prognosis, Immunotherapy, and Chemotherapy in LIHC: A Comprehensive Pan-Cancer Analysis and Experimental Validation.Journal of Cancer · 2026Article
- Phosphorylation of RNF213 by ATM-mediated ubiquitination of RPA1 regulates homologous recombination repair and chemosensitivity.Cell death & disease · 2025Article
- Loss of Nuclear Profilin 1 Triggers Oncogenic Reprogramming of Mammary Epithelial Cells Through Dysregulated DNA Replication in Breast Cancer.Journal of breast cancer · 2025Article
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- RNF20-mediated H2B monoubiquitination protects stalled forks from degradation and promotes fork restart.EMBO reports · 2025Article
- Centromere-size reduction and chromatin state dynamics following intergenomic hybridization in cotton.PLoS genetics · 2025Article
- Phospho-TRIM21 orchestrates RPA2 ubiquitination switch to promote homologous recombination and tumor radio/chemo-resistance.Oncogene · 2025Article
- RNF20 dual regulation of MDA5 signaling to maintain immune homeostasis in chickens.Journal of virology · 2025Article
- Investigating synthetic lethality and PARP inhibitor resistance in pancreatic cancer through enantiomer differential activity.Cell death discovery · 2025Article
- EHMT2-mediated R-loop formation promotes the malignant progression of prostate cancer via activating Aurora B.Clinical and translational medicine · 2025Article
- Structural and functional characterisation and regulatory mechanisms of SWI/SNF and RSC chromatin remodelling complexes in fungi.Mycology · 2025Review
- USP3 promotes DNA damage response and chemotherapy resistance through stabilizing and deubiquitinating SMARCA5 in prostate cancer.Cell death & disease · 2024Article
- PRMT1 inhibition perturbs RNA metabolism and induces DNA damage in clear cell renal cell carcinoma.Nature communications · 2024Article
- The Rtf1/Prf1-dependent histone modification axis counteracts multi-drug resistance in fission yeast.Life science alliance · 2024Article
- The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024Review
- Maintaining chromosome and genome stability by the RPA-RNF20-SNF2H cascade.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human tumor suppressor Ring finger protein 20 (RNF20)-mediated histone H2B monoubiquitination (H2Bub) is essential for proper chromosome segregation and DNA repair. However, what is the precise function and mechanism of RNF20-H2Bub in chromosome segregation and how this pathway is activated to preserve genome stability remain unknown. Here, we show that the single-strand DNA-binding factor Replication protein A (RPA) interacts with RNF20 mainly in the S and G2/M phases and recruits RNF20 to mitotic centromeres in a centromeric R-loop-dependent manner. In parallel, RPA recruits RNF20 to chromosomal breaks upon DNA damage. Disruption of the RPA-RNF20 interaction or depletion of RNF20 increases mitotic lagging chromosomes and chromosome bridges and impairs BRCA1 and RAD51 loading and homologous recombination repair, leading to elevated chromosome breaks, genome instability, and sensitivities to DNA-damaging agents. Mechanistically, the RPA-RNF20 pathway promotes local H2Bub, H3K4 dimethylation, and subsequent SNF2H recruitment, ensuring proper Aurora B kinase activation at centromeres and efficient loading of repair proteins at DNA breaks. Thus, the RPA-RNF20-SNF2H cascade plays a broad role in preserving genome stability by coupling H2Bub to chromosome segregation and DNA repair.
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