ArticleOncogene2025
Phospho-TRIM21 orchestrates RPA2 ubiquitination switch to promote homologous recombination and tumor radio/chemo-resistance.
Article in Oncogene, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- TRIM21-mediated ubiquitination of PARP1 regulated by the PI3K/AKT-STAT5A axis suppresses small cell lung cancer.Nature communications · 2026Article
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Authors and funding
11 authors.
Funding
Abstract
RPA2, a key component of the RPA complex, is essential for single-stranded DNA (ssDNA) binding and DNA repair. However, the regulation of RPA2-ssDNA interaction and the recruitment of repair proteins following DNA damage remain incompletely understood. Our study uncovers a novel mechanism by which phosphorylated TRIM21 (Phospho-TRIM21) regulates RPA2 ubiquitination, thereby modulating homologous recombination and tumor radio/chemo-resistance. In the absence of DNA damage, TRIM21 mediates K63-linked ubiquitination of RPA2, countering K6-linked ubiquitination. Upon DNA damage, ubiquitination-modified RPA2 binds ssDNA, stabilizing the DNA structure and facilitating ATRIP/ATR recruitment. ATR subsequently phosphorylates TRIM21 at Ser41, leading to the dissociation of the TRIM21-RPA2 complex and a shift in RPA2 ubiquitination from K63 to K6 linkage. This shift maintains RPA2 ubiquitination homeostasis and stabilizes the RPA2-ATRIP complex, which is crucial for efficient homologous recombination (HR) repair and enhanced tumor radio/chemo-resistance. We also demonstrate that TRIM21 is frequently upregulated in cancers, and its depletion sensitizes cancer cells to radio/chemotherapy, suggesting its potential as a therapeutic target. This study provides novel insights into TRIM21's role in the DNA damage response and its implications for cancer treatment.
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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.