ArticleProceedings of the National Academy of Sciences of the United States of America2024
PARP1 UFMylation ensures the stability of stalled replication forks.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Discovery and Characterization of Inhibitors of Ubiquitin-Like Modifier Activating Enzyme 5 (UBA5): Targeting the UFMylation Pathway in Cancer and Neurodegenerative Diseases.ACS chemical biology · 2026Article
- Narrative review-the emerging role, functions, and mechanisms of UFMylation in cancers.Translational cancer research · 2026Review
- Systematic discovery of UFM1 receptors reveals a regulatory module in DNA repair directing non-homologous end-joining.Nature communications · 2026Article
- The mechanistic basis and cellular functions of UFMylation.Nature reviews. Molecular cell biology · 2026Review
- Cooperative molecular interaction networks govern PARP1 inhibitor selectivity and binding affinity.PLoS computational biology · 2026Article
- Optimization of protein UFMylation modification method and its application in substrate identification in human cells.The Journal of biological chemistry · 2026Article
- A genus-wide interaction atlas across NS4B orthologues identifies a conserved role for UFMylation in orthoflavivirus replication.Nature communications · 2026Article
- ZOMES: expanding roles of the PCI complexes from protein metabolism to drug discovery.npj metabolic health and disease · 2026Article
- The UFL1-AKT positive feedback loop promotes breast cancer progression by enhancing lipid synthesis.Nature communications · 2026Article
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- Unveiling the hidden regulators: how post-translational modifications influence the progression and treatment of hepatocellular carcinoma.Frontiers in oncology · 2026Review
- Decoding replication stress responses through post-translational modifications.Nature chemical biology · 2025Review
- UFMylation System: Biological Functions, Molecular Mechanisms, Diseases, and Drug Discovery.MedComm · 2025Review
- Akt-phosphorylated UFL1 UFMylates ArpC4 to promote metastasis.Nature structural & molecular biology · 2025Article
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- Multifaceted roles of UFMylation in health and disease.Acta pharmacologica Sinica · 2025Review
- The role of extrachromosomal DNA in tumorigenesis and progression.Frontiers in oncology · 2025Review
- The emerging roles of UFMylation in the modulation of immune responses.Clinical and translational medicine · 2024Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The S-phase checkpoint involving CHK1 is essential for fork stability in response to fork stalling. PARP1 acts as a sensor of replication stress and is required for CHK1 activation. However, it is unclear how the activity of PARP1 is regulated. Here, we found that UFMylation is required for the efficient activation of CHK1 by UFMylating PARP1 at K548 during replication stress. Inactivation of UFL1, the E3 enzyme essential for UFMylation, delayed CHK1 activation and inhibits nascent DNA degradation during replication blockage as seen in PARP1-deficient cells. An in vitro study indicated that PARP1 is UFMylated at K548, which enhances its catalytic activity. Correspondingly, a PARP1 UFMylation-deficient mutant (K548R) and pathogenic mutant (F553L) compromised CHK1 activation, the restart of stalled replication forks following replication blockage, and chromosome stability. Defective PARP1 UFMylation also resulted in excessive nascent DNA degradation at stalled replication forks. Finally, we observed that PARP1 UFMylation-deficient knock-in mice exhibited increased sensitivity to replication stress caused by anticancer treatments. Thus, we demonstrate that PARP1 UFMylation promotes CHK1 activation and replication fork stability during replication stress, thus safeguarding genome integrity.
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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.