ArticleOncogene2015
Rad18 and Rnf8 facilitate homologous recombination by two distinct mechanisms, promoting Rad51 focus formation and suppressing the toxic effect of nonhomologous end joining.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Targeting Genome Maintenance Defects of Cancers Using Chain-Terminating Nucleoside Analogs.Cancer science · 2026Review
- ADAR1 enhances tumor proliferation and radioresistance in non-small cell lung cancer by interacting with Rad18.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- DNA damage repair factor Rad18 controls virulence partially via transcriptional suppression of genesVirulence · 2024Article
- RAD18- and BRCA1-dependent pathways promote cellular tolerance to the nucleoside analog ganciclovir.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin.Nucleic acids research · 2024Article
- REV3 promotes cellular tolerance to 5-fluorodeoxyuridine by activating translesion DNA synthesis and intra-S checkpoint.PLoS genetics · 2024Article
- RAD18 O-GlcNAcylation promotes translesion DNA synthesis and homologous recombination repair.Cell death & disease · 2024Article
- The proofreading exonuclease of leading-strand DNA polymerase epsilon prevents replication fork collapse at broken template strands.Nucleic acids research · 2023Article
- RAD18 opposes transcription-associated genome instability through FANCD2 recruitment.PLoS genetics · 2022Article
- RAD18 confers radioresistance of esophagus squamous cell carcinoma through regulating p-DNA-PKcs.Cancer medicine · 2022Article
- LncRNA CTBP1-DT-encoded microprotein DDUP sustains DNA damage response signalling to trigger dual DNA repair mechanisms.Nucleic acids research · 2022Article
- Genome-wide CRISPR screen identified Rad18 as a determinant of doxorubicin sensitivity in osteosarcoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos.Nucleic acids research · 2022Article
- Phosphoproteomics reveals that cinobufotalin promotes intrahepatic cholangiocarcinoma cell apoptosis by activating the ATM/CHK2/p53 signaling pathway.Frontiers in oncology · 2022Article
- Few-shot learning creates predictive models of drug response that translate from high-throughput screens to individual patients.Nature cancer · 2021Article
- Stimulation of CRISPR-mediated homology-directed repair by an engineered RAD18 variant.Nature communications · 2019Article
- Review
- Chromatin remodeler ALC1 prevents replication-fork collapse by slowing fork progression.PloS one · 2018Article
- Article
- Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides.Cell cycle (Georgetown, Tex.) · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The E2 ubiquitin conjugating enzyme Ubc13 and the E3 ubiquitin ligases Rad18 and Rnf8 promote homologous recombination (HR)-mediated double-strand break (DSB) repair by enhancing polymerization of the Rad51 recombinase at γ-ray-induced DSB sites. To analyze functional interactions between the three enzymes, we created RAD18(-/-), RNF8(-/-), RAD18(-/-)/RNF8(-/-) and UBC13(-/-)clones in chicken DT40 cells. To assess the capability of HR, we measured the cellular sensitivity to camptothecin (topoisomerase I poison) and olaparib (poly(ADP ribose)polymerase inhibitor) because these chemotherapeutic agents induce DSBs during DNA replication, which are repaired exclusively by HR. RAD18(-/-), RNF8(-/-) and RAD18(-/-)/RNF8(-/-) clones showed very similar levels of hypersensitivity, indicating that Rad18 and Rnf8 operate in the same pathway in the promotion of HR. Although these three mutants show less prominent defects in the formation of Rad51 foci than UBC13(-/-)cells, they are more sensitive to camptothecin and olaparib than UBC13(-/-)cells. Thus, Rad18 and Rnf8 promote HR-dependent repair in a manner distinct from Ubc13. Remarkably, deletion of Ku70, a protein essential for nonhomologous end joining (NHEJ) significantly restored tolerance of RAD18(-/-) and RNF8(-/-) cells to camptothecin and olaparib without affecting Rad51 focus formation. Thus, in cellular tolerance to the chemotherapeutic agents, the two enzymes collaboratively promote DSB repair by HR by suppressing the toxic effect of NHEJ on HR rather than enhancing Rad51 focus formation. In contrast, following exposure to γ-rays, RAD18(-/-), RNF8(-/-), RAD18(-/-)/RNF8(-/-) and UBC13(-/-)cells showed close correlation between cellular survival and Rad51 focus formation at DSB sites. In summary, the current study reveals that Rad18 and Rnf8 facilitate HR by two distinct mechanisms: suppression of the toxic effect of NHEJ on HR during DNA replication and the promotion of Rad51 focus formation at radiotherapy-induced DSB sites.
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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.