ArticleCell2012
TRIP12 and UBR5 suppress spreading of chromatin ubiquitylation at damaged chromosomes.
Article in Cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 242 papers.
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
242 citing papers in PubMed, 339 citations in OpenAlex.
- A massively parallel CRISPR-based screening platform for modifiers of neuronal depolarization.Nature communications · 2026Article
- USP28 Deficiency is Linked to Impaired Ubiquitin-dependent Proteostasis in Huntington's Disease.Molecular neurobiology · 2026Article
- Chromatin association promotes UBR5-mediated degradation of Rb.bioRxiv : the preprint server for biology · 2026Article
- HECT ubiquitin ligases as regulators of inflammatory signalling.Cell death and differentiation · 2026Review
- Deciphering the Ubiquitin-like Code of DNA-PK: Mechanisms and Therapeutic Opportunities.Biomolecules · 2026Review
- The TRIP12's intrinsically disordered region induces chromatin condensates and interferes with nuclear processes.iScience · 2026Article
- DUX4-induced HSATII RNA accumulation drives protein aggregation, impacting RNA processing pathways.The Journal of cell biology · 2026Article
- Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.Nature communications · 2026Article
- The mutual regulation of SOX12 and RNF168 modulates cisplatin resistance in esophageal squamous cell carcinoma cells by regulating DNA damage repair.Cell & bioscience · 2026Article
- miR-381-3p suppresses pterygium progression by regulating HACE1/TRIP12-mediated ubiquitin-degradation of MCPIP1.In vitro cellular & developmental biology. Animal · 2026Article
- E3 ubiquitin ligases: structural diversity, dysregulation in disease, and their emerging role in targeted therapeutic strategies.Frontiers in molecular biosciences · 2026Review
- E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.Frontiers in oncology · 2026Review
- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- Ubiquitination of TFEB increased intestinal permeability to aggravate metabolic dysfunction-associated steatohepatitis.Hepatology (Baltimore, Md.) · 2025Article
- Functional landscape of ubiquitin linkages couples K29-linked ubiquitylation to epigenome integrity.The EMBO journal · 2025Article
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- Article
- Nuclear ubiquitination permits Hippo-YAP signal for liver development and tumorigenesis.Nature chemical biology · 2025Article
- TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains.Nature structural & molecular biology · 2025Article
- ZNF451 collaborates with RNF8 to regulate RNF168 localization and amplify ubiquitination signaling to promote DNA damage repair and regulate radiosensitivity.Cell death and differentiation · 2025Article
182 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
18 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone ubiquitylation is a prominent response to DNA double-strand breaks (DSBs), but how these modifications are confined to DNA lesions is not understood. Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1. Thus, regulatory and proteolytic ubiquitylations are wired in a self-limiting circuit that promotes histone ubiquitylation near the DNA lesions but at the same time counteracts its excessive spreading to undamaged chromosomes. We provide evidence that this mechanism is vital for the homeostasis of ubiquitin-controlled events after DNA breakage and can be subverted during tumorigenesis.
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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.