ArticleMolecular cell2023
ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 53 citations in OpenAlex.
- Nuclear mechanobiology: a brief history and five unresolved questions.Nucleus (Austin, Tex.) · 2026Article
- DONSON links tumor-cell survival to MIF-associated macrophage remodeling in small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Immune response to DNA and RNA: structural insights, molecular mechanisms, and therapeutic targeting.Molecular biomedicine · 2026Review
- The KAT8-CDK1 K33 acetylation axis drives doxorubicin resistance by suppressing ferroptosis and apoptosis in breast cancer.Cell death & disease · 2026Article
- Tumorigenesis of well-differentiated and dedifferentiated liposarcoma: 12q amplicon architecture, oncogenic cargo, and evolutionary progression.Cancer metastasis reviews · 2026Review
- Chromosomal Instability Drives Glioblastoma Heterogeneity and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- Detection of nuclear STING in cultured human cells and in the normal and cancer tissues.iScience · 2026Article
- Bi-allelic WDHD1 variants cause microcephalic primordial dwarfism.American journal of human genetics · 2026Article
- Fertilization with Protamine-2 deficient sperm triggers abnormal pronucleus development and zygotic cleavage†.Biology of reproduction · 2026Article
- Roles of DNA Damage Response Pathway in the Regulation of the Nuclear Envelope.Current issues in molecular biology · 2026Review
- Review
- Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels.Nature communications · 2025Article
- ATR promotes genome instability via CENP-A eviction from centromeres under replication stress.bioRxiv : the preprint server for biology · 2025Article
- Mitotic DNA repair by TMEJ suppresses replication stress-induced nuclear envelope reassembly defect.Nature communications · 2025Article
- Cancer-associated SPOP mutations enlarge nuclear size and facilitate nuclear envelope rupture upon farnesyltransferase inhibitor treatment.The Journal of clinical investigation · 2025Article
- Nuclear and genome dynamics underlying DNA double-strand break repair.Nature reviews. Molecular cell biology · 2025Review
- Nuclear deformability increases PARPi sensitivity in BRCA1-deficient cells by increasing microtubule-dependent DNA break mobility.Nature communications · 2025Article
- Image-based identification and isolation of micronucleated cells to dissect cellular consequences.eLife · 2025Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The human ataxia telangiectasia mutated and Rad3-related (ATR) kinase functions in the nucleus to protect genomic integrity. Micronuclei (MN) arise from genomic and chromosomal instability and cause aneuploidy and chromothripsis, but how MN are removed is poorly understood. Here, we show that ATR is active in MN and promotes their rupture in S phase by phosphorylating Lamin A/C at Ser395, which primes Ser392 for CDK1 phosphorylation and destabilizes the MN envelope. In cells harboring MN, ATR or CDK1 inhibition reduces MN rupture. Consequently, ATR inhibitor (ATRi) diminishes activation of the cytoplasmic DNA sensor cGAS and compromises cGAS-dependent autophagosome accumulation in MN and clearance of micronuclear DNA. Furthermore, ATRi reduces cGAS-mediated senescence and killing of MN-bearing cancer cells by natural killer cells. Thus, in addition to the canonical ATR signaling pathway, an ATR-CDK1-Lamin A/C axis promotes MN rupture to clear damaged DNA and cells, protecting the genome in cell populations through unexpected cell-autonomous and cell-non-autonomous mechanisms.
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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.