ArticleProceedings of the National Academy of Sciences of the United States of America2015
Loss of autophagy causes a synthetic lethal deficiency in DNA repair.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
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Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- CRISPR screen identifies autophagy inhibition (GNS561) as a PARP inhibitor (AZD5305) combination strategy in small cell lung cancer.Cancer & metabolism · 2026Article
- Dynamins maintain nuclear envelope homeostasis and genome stability.Nature communications · 2026Article
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- AoChk1 Is Required for Sporulation, Trap Formation, and Metabolic Process inJournal of fungi (Basel, Switzerland) · 2025Article
- The Role of Intermittent Fasting in the Activation of Autophagy Processes in the Context of Cancer Diseases.International journal of molecular sciences · 2025Review
- Autophagy induction enhances homologous recombination-associated CRISPR-Cas9 gene editing.Nucleic acids research · 2025Article
- p62/SQSTM1 in cancer: phenomena, mechanisms, and regulation in DNA damage repair.Cancer metastasis reviews · 2025Review
- Beclin 1-Mediated Autophagy Is Potentiated by an Interaction with the Neuronal Adaptor FE65.Biology · 2025Article
- CS-6-induced p62 accumulation exacerbates DNA damage in colorectal cancer.Frontiers in pharmacology · 2025Article
- The interplay between DNA damage response and mitochondrial dysfunction in radiotherapy.Frontiers in oncology · 2025Review
- Targeting the HECTD3-p62 axis increases the radiosensitivity of triple negative breast cancer cells.Cell death discovery · 2024Article
- An interpretable artificial intelligence framework for designing synthetic lethality-based anti-cancer combination therapies.Journal of advanced research · 2024Article
- Repeated radon exposure induced ATM kinase-mediated DNA damage response and protective autophagy in mice and human bronchial epithelial cells.Toxicology research · 2024Article
- Complex Interplay between DNA Damage and Autophagy in Disease and Therapy.Biomolecules · 2024Review
- Chemotherapy's effects on autophagy in the treatment of Hodgkin's lymphoma: a scoping review.Discover oncology · 2024Article
- Role of Tumor Cell Intrinsic and Host Autophagy in Cancer.Cold Spring Harbor perspectives in medicine · 2024Review
- NBR1-mediated selective autophagy of ARF7 modulates root branching.EMBO reports · 2024Article
- LC3B drives transcription-associated homologous recombination via direct interaction with R-loops.Nucleic acids research · 2024Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
(Macro)autophagy delivers cellular constituents to lysosomes for degradation. Although a cytoplasmic process, autophagy-deficient cells accumulate genomic damage, but an explanation for this effect is currently unclear. We report here that inhibition of autophagy causes elevated proteasomal activity leading to enhanced degradation of checkpoint kinase 1 (Chk1), a pivotal factor for the error-free DNA repair process, homologous recombination (HR). We show that loss of autophagy critically impairs HR and that autophagy-deficient cells accrue micronuclei and sub-G1 DNA, indicators of diminished genomic integrity. Moreover, due to impaired HR, autophagy-deficient cells are hyperdependent on nonhomologous end joining (NHEJ) for repair of DNA double-strand breaks. Consequently, inhibition of NHEJ following DNA damage in the absence of autophagy results in persistence of genomic lesions and rapid cell death. Because autophagy deficiency occurs in several diseases, these findings constitute an important link between autophagy and DNA repair and highlight a synthetic lethal strategy to kill autophagy-deficient cells.
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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.