ArticleGenes & development2012
SUMO-targeted ubiquitin E3 ligase RNF4 is required for the response of human cells to DNA damage.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.
What it found
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Who cites it
165 citing papers in PubMed, 234 citations in OpenAlex.
- GNL3 SUMOylation is essential for DNA double-strand break repair by homologous recombination.Nature communications · 2026Article
- ROS-SUMO Crosstalk in Oxidative Stress: Disease Mechanisms and Reproductive Health.Antioxidants (Basel, Switzerland) · 2026Review
- Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.Cellular and molecular life sciences : CMLS · 2026Review
- SUMOylation is destined for regulatory T cell-related immune dysregulation.Cell death discovery · 2026Review
- Targeting ATR-CHK1 and ATM-CHK2 Axes in Pancreatic Cancer-A Comprehensive Review of Literature.International journal of molecular sciences · 2026Review
- E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.Frontiers in oncology · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- DNA double strand break repair: a model of specificity and complexity in SUMO signalling.Essays in biochemistry · 2025Review
- Cysteine-reactive covalent chloro-N-acetamide ligands induce ferroptosis mediated cell death.EMBO reports · 2025Article
- PIN1-SUMO2/3 motif suppresses excessive RNF168 chromatin accumulation and ubiquitin signaling to promote IR resistance.Nature communications · 2025Article
- SUMO-targeted Ubiquitin Ligases as crucial mediators of protein homeostasis in Candida glabrata.PLoS pathogens · 2024Article
- The role of SUMOylation in biomolecular condensate dynamics and protein localization.Cell insight · 2024Review
- ATXN3: a multifunctional protein involved in the polyglutamine disease spinocerebellar ataxia type 3.Expert reviews in molecular medicine · 2024Review
- Crosstalk between SUMOylation and other post-translational modifications in breast cancer.Cellular & molecular biology letters · 2024Review
- E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease.The Biochemical journal · 2024Review
- SUMO and the DNA damage response.Biochemical Society transactions · 2024Review
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication.The Journal of clinical investigation · 2024Article
- The ubiquitin codes in cellular stress responses.Protein & cell · 2024Review
- Review
105 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
6 authors at 3 institutions in 1 country.
Funding
Abstract
Here we demonstrate that RNF4, a highly conserved small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, plays a critical role in the response of mammalian cells to DNA damage. Human cells in which RNF4 expression was ablated by siRNA or chicken DT40 cells with a homozygous deletion of the RNF4 gene displayed increased sensitivity to DNA-damaging agents. Recruitment of RNF4 to double-strand breaks required its RING and SUMO interaction motif (SIM) domains and DNA damage factors such as NBS1, mediator of DNA damage checkpoint 1 (MDC1), RNF8, 53BP1, and BRCA1. In the absence of RNF4, these factors were still recruited to sites of DNA damage, but 53BP1, RNF8, and RNF168 displayed delayed clearance from such foci. SILAC-based proteomics of SUMO substrates revealed that MDC1 was SUMO-modified in response to ionizing radiation. As a consequence of SUMO modification, MDC1 recruited RNF4, which mediated ubiquitylation at the DNA damage site. Failure to recruit RNF4 resulted in defective loading of replication protein A (RPA) and Rad51 onto ssDNA. This appeared to be a consequence of reduced recruitment of the CtIP nuclease, resulting in inefficient end resection. Thus, RNF4 is a novel DNA damage-responsive protein that plays a role in homologous recombination and integrates SUMO modification and ubiquitin signaling in the cellular response to genotoxic stress.
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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.