ArticleGenome instability & disease2022
Dynamic recruitment of UFM1-specific peptidase 2 to the DNA double-strand breaks regulated by WIP1.
Article in Genome instability & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Recent Advances in Therapy for the Neurodegenerative Disorder Ataxia-Telangiectasia.International journal of molecular sciences · 2026Review
- UFMylation of Pyruvate Dehydrogenase Regulates Mitochondrial Metabolism.bioRxiv : the preprint server for biology · 2026Article
- MCM5 UFMylation regulates replication origin firing and fork progression.The EMBO journal · 2025Article
- UFMylation System: Biological Functions, Molecular Mechanisms, Diseases, and Drug Discovery.MedComm · 2025Review
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- UFMylation: A Potential Modification for Neurological Diseases.Current neuropharmacology · 2025Review
- The UFMylation pathway is impaired in Alzheimer's disease.Molecular neurodegeneration · 2024Article
- The UFMylation pathway is impaired in Alzheimer's disease.bioRxiv : the preprint server for biology · 2024Article
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- Review
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Authors and funding
6 authors.
Funding
Abstract
The ufmylation ligase-UFL1 promotes ATM activation by monoufmylating H4 at K31 in a positive-feedback loop after double-strand breaks (DSB) occur, whereas UFM1 Specific Peptidase 2 (UfSP2) suppresses ATM activation, but the mechanism of recruitment of UfSP2 to the DSB finetuning DNA damage response is still not clear. Here, we report that UfSP2 foci formation is delayed compared to UFL1 foci formation following the radiation insult. Mechanistically, UfSP2 binds to the MRN complex in absence of DSB. Irradiation-induced phosphorylation of UfSP2 by ATM leads to the dissociation of UfSP2 from the MRN complex. This phosphorylation can be removed by the phosphatase WIP1, thereby UfSP2 is recruited to the DSBs, deufmylating H4 and suppressing ATM activation. In summary, we identify a mechanism of delicately negative modulation of ATM activation by UfSP2 and rewires ATM activation pathways.
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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.