ArticlePloS one2013
ATM deficiency results in accumulation of DNA-topoisomerase I covalent intermediates in neural cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 67 citations in OpenAlex.
- Increased genomic instability following treatment with direct acting anti-hepatitis C virus drugs.EBioMedicine · 2018Trial
- Molecular Determinants of Response and Rational Drug Combinations for Antibody-Drug Conjugates (ADCs) with Topoisomerase I (TOP1) Inhibitor Payloads.Journal of molecular biology · 2026Review
- A comparative study of different antiviral treatment protocols in HCV related cryoglobulinemic vasculitis.Scientific reports · 2024Article
- A-T neurodegeneration and DNA damage-induced transcriptional stress.DNA repair · 2024Review
- SPRTN-dependent DPC degradation precedes repair of damaged DNA: a proof of concept revealed by the STAR assay.Nucleic acids research · 2023Article
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- Defective repair of topoisomerase I induced chromosomal damage in Huntington's disease.Cellular and molecular life sciences : CMLS · 2022Article
- The Complex Mechanisms by Which Neurons Die Following DNA Damage in Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- TEX264 at the intersection of autophagy and DNA repair.Autophagy · 2022Review
- Cellular functions of the protein kinase ATM and their relevance to human disease.Nature reviews. Molecular cell biology · 2021Review
- DNA damage as a mechanism of neurodegeneration in ALS and a contributor to astrocyte toxicity.Cellular and molecular life sciences : CMLS · 2021Review
- Poly-ADP-ribosylation drives loss of protein homeostasis in ATM and Mre11 deficiency.Molecular cell · 2021Article
- The DNA damage inducible lncRNA SCAT7 regulates genomic integrity and topoisomerase 1 turnover in lung adenocarcinoma.NAR cancer · 2021Article
- Tdp1 protects from topoisomerase 1-mediated chromosomal breaks in adult zebrafish but is dispensable during larval development.Science advances · 2021Article
- Topoisomerase-Mediated DNA Damage in Neurological Disorders.Frontiers in aging neuroscience · 2021Review
- Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair.Nucleic acids research · 2020Article
- Tyrosyl-DNA Phosphodiesterase I N-Terminal Domain Modifications and Interactions Regulate Cellular Function.Genes · 2019Review
- Review
- FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I-induced DNA breakage and transcriptional stress.Life science alliance · 2019Article
- DNA damage and transcriptional regulation in iPSC-derived neurons from Ataxia Telangiectasia patients.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Accumulation of peptide-linked DNA breaks contributes to neurodegeration in humans. This is typified by defects in tyrosyl DNA phosphodiesterase 1 (TDP1) and human hereditary ataxia. TDP1 primarily operates at single-strand breaks (SSBs) created by oxidative stress or by collision of transcription machinery with topoisomerase I intermediates (Top1-CCs). Cellular and cell-free studies have shown that Top1 at stalled Top1-CCs is first degraded to a small peptide resulting in Top1-SSBs, which are the primary substrates for TDP1. Here we established an assay to directly compare Top1-SSBs and Top1-CCs. We subsequently employed this assay to reveal an increased steady state level of Top1-CCs in neural cells lacking Atm; the protein mutated in ataxia telangiectasia. Our data suggest that the accumulation of endogenous Top1-CCs in Atm-/- neural cells is primarily due to elevated levels of reactive oxygen species. Biochemical purification of Top1-CCs from neural cell extract and the use of Top1 poisons further confirmed a role for Atm during the formation/resolution of Top1-CCs. Finally, we report that global transcription is reduced in Atm-/- neural cells and fails to recover to normal levels following Top1-mediated DNA damage. Together, these data identify a distinct role for ATM during the formation/resolution of neural Top1-CCs and suggest that their accumulation contributes to the neuropathology of ataxia telangiectasia.
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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.