ArticleCommunications biology2023
ANKLE1 cleaves mitochondrial DNA and contributes to cancer risk by promoting apoptosis resistance and metabolic dysregulation.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Neurotoxicity, α-synuclein pathology, and mitochondrial dysfunction: A comparative study of different mouse models of Parkinson's disease.Neural regeneration research · 2026Article
- Nuclear envelope proteins in cancer: revisiting the significance of LEM-domain proteins.Frontiers in cell and developmental biology · 2026Review
- ANKLE1 processes chromatin bridges by cleaving mechanically stressed DNA.Nature communications · 2025Article
- Donor genetics and storage conditions influence mitochondrial DNA and extracellular vesicle levels in RBC units.JCI insight · 2025Article
- Functional dissection of the conserved C. elegans LEM-3/ANKLE1 nuclease reveals a crucial requirement for the LEM-like and GIY-YIG domains for DNA bridge processing.Nucleic acids research · 2025Article
- Molecular functions of ANKLE2 and its implications in human disease.Disease models & mechanisms · 2024Review
- Mitochondrial DNA-targeted therapy: A novel approach to combat cancer.Cell insight · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Alleles within the chr19p13.1 locus are associated with increased risk of both ovarian and breast cancer and increased expression of the ANKLE1 gene. ANKLE1 is molecularly characterized as an endonuclease that efficiently cuts branched DNA and shuttles between the nucleus and cytoplasm. However, the role of ANKLE1 in mammalian development and homeostasis remains unknown. In normal development ANKLE1 expression is limited to the erythroblast lineage and we found that ANKLE1's role is to cleave the mitochondrial genome during erythropoiesis. We show that ectopic expression of ANKLE1 in breast epithelial-derived cells leads to genome instability and mitochondrial DNA (mtDNA) cleavage. mtDNA degradation then leads to mitophagy and causes a shift from oxidative phosphorylation to glycolysis (Warburg effect). Moreover, mtDNA degradation activates STAT1 and expression of epithelial-mesenchymal transition (EMT) genes. Reduction in mitochondrial content contributes to apoptosis resistance, which may allow precancerous cells to avoid apoptotic checkpoints and proliferate. These findings provide evidence that ANKLE1 is the causal cancer susceptibility gene in the chr19p13.1 locus and describe mechanisms by which higher ANKLE1 expression promotes cancer risk.
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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.