ArticleCell death and differentiation2013
RNF4 is required for DNA double-strand break repair in vivo.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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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
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- GNL3 SUMOylation is essential for DNA double-strand break repair by homologous recombination.Nature communications · 2026Article
- SUMOylation is destined for regulatory T cell-related immune dysregulation.Cell death discovery · 2026Review
- DNA double strand break repair: a model of specificity and complexity in SUMO signalling.Essays in biochemistry · 2025Review
- Interaction networks of SIM-binding groove mutants reveal alternate modes of SUMO binding and profound impact on SUMO conjugation.Science advances · 2025Article
- SUMO2/3 modification of transcription-associated proteins controls cell viability in response to oxygen and glucose deprivation-mediated stress.Cell death discovery · 2025Article
- PIN1-SUMO2/3 motif suppresses excessive RNF168 chromatin accumulation and ubiquitin signaling to promote IR resistance.Nature communications · 2025Article
- Multifaceted roles of SUMO in DNA metabolism.Nucleus (Austin, Tex.) · 2024Review
- The role of SUMOylation in biomolecular condensate dynamics and protein localization.Cell insight · 2024Review
- SUMO and the DNA damage response.Biochemical Society transactions · 2024Review
- Review
- SENP5 promotes homologous recombination-mediated DNA damage repair in colorectal cancer cells through H2AZ deSUMOylation.Journal of experimental & clinical cancer research : CR · 2023Article
- Beyond canonical PROTAC: biological targeted protein degradation (bioTPD).Biomaterials research · 2023Review
- SUMOylation-mediated PSME3-20Science advances · 2023Article
- RNF4~RGMb~BMP6 axis required for osteogenic differentiation and cancer cell survival.Cell death & disease · 2022Article
- Crosstalk between SUMOylation and ubiquitylation controls DNA end resection by maintaining MRE11 homeostasis on chromatin.Nature communications · 2022Article
- RNF4 controls the extent of replication fork reversal to preserve genome stability.Nucleic acids research · 2022Article
- DNA damage-induced degradation of Sp1 promotes cellular senescence.GeroScience · 2022Article
- RNF4 silencing induces cell growth arrest and DNA damage by promoting nuclear targeting of p62 in hepatocellular carcinoma.Oncogene · 2022Article
- Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Unrepaired DNA double-strand breaks (DSBs) cause genetic instability that leads to malignant transformation or cell death. Cells respond to DSBs with the ordered recruitment of signaling and repair proteins to the sites of DNA lesions. Coordinated protein SUMOylation and ubiquitylation have crucial roles in regulating the dynamic assembly of protein complexes at these sites. However, how SUMOylation influences protein ubiquitylation at DSBs is poorly understood. We show herein that Rnf4, an E3 ubiquitin ligase that targets SUMO-modified proteins, accumulates in DSB repair foci and is required for both homologous recombination (HR) and non-homologous end joining repair. To establish a link between Rnf4 and the DNA damage response (DDR) in vivo, we generated an Rnf4 allelic series in mice. We show that Rnf4-deficiency causes persistent ionizing radiation-induced DNA damage and signaling, and that Rnf4-deficient cells and mice exhibit increased sensitivity to genotoxic stress. Mechanistically, we show that Rnf4 targets SUMOylated MDC1 and SUMOylated BRCA1, and is required for the loading of Rad51, an enzyme required for HR repair, onto sites of DNA damage. Similarly to inactivating mutations in other key regulators of HR repair, Rnf4 deficiency leads to age-dependent impairment in spermatogenesis. These findings identify Rnf4 as a critical component of the DDR in vivo and support the possibility that Rnf4 controls protein localization at DNA damage sites by integrating SUMOylation and ubiquitylation events.
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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.