ArticleMolecular cell2021
Poly-ADP-ribosylation drives loss of protein homeostasis in ATM and Mre11 deficiency.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Molecular Characterization of PARP Inhibitor Response Reveals Co-Targeting Strategies in Advanced Prostate Cancer.Cancers · 2026Article
- Targeting the FNIP2-SERCA2b axis improves metabolic and mitochondrial defects in Ataxia Telangiectasia.Cell death & disease · 2026Article
- Epigenetic consequences of DNA damage.Molecular cell · 2026Review
- Positive selection analyses identify a single WWE domain residue that shapes ZAP into a more potent restriction factor against alphaviruses.PLoS pathogens · 2024Article
- Senataxin deficiency disrupts proteostasis through nucleolar ncRNA-driven protein aggregation.The Journal of cell biology · 2024Article
- Genome-wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression.Genome biology · 2024Article
- Regulation of transcription patterns, poly(ADP-ribose), and RNA-DNA hybrids by the ATM protein kinase.Cell reports · 2024Article
- Glioblastoma and its treatment are associated with extensive accelerated brain aging.Aging cell · 2024Article
- A-T neurodegeneration and DNA damage-induced transcriptional stress.DNA repair · 2024Review
- cGAS-STING signalling regulates microglial chemotaxis in genome instability.Nucleic acids research · 2024Article
- Multifaceted Role of PARP1 in Maintaining Genome Stability Through Its Binding to Alternative DNA Structures.Journal of molecular biology · 2024Review
- The DNA repair kinase ATM regulates CD13 expression and cell migration.Frontiers in cell and developmental biology · 2024Article
- Regulation of transcription patterns, poly-ADP-ribose, and RNA-DNA hybrids by the ATM protein kinase.bioRxiv : the preprint server for biology · 2023Article
- Hypoxia-induced transcriptional stress is mediated by ROS-induced R-loops.Nucleic acids research · 2023Article
- Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony.Cellular and molecular life sciences : CMLS · 2023Review
- The Complex Network of ADP-Ribosylation and DNA Repair: Emerging Insights and Implications for Cancer Therapy.International journal of molecular sciences · 2023Review
- Article
- Regulation of Biomolecular Condensates by Poly(ADP-ribose).Chemical reviews · 2023Review
- DNA Damage-Mediated Neurotoxicity in Parkinson's Disease.International journal of molecular sciences · 2023Review
- PARP1 associates with R-loops to promote their resolution and genome stability.Nucleic acids research · 2023Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
Loss of the ataxia-telangiectasia mutated (ATM) kinase causes cerebellum-specific neurodegeneration in humans. We previously demonstrated that deficiency in ATM activation via oxidative stress generates insoluble protein aggregates in human cells, reminiscent of protein dysfunction in common neurodegenerative disorders. Here, we show that this process is driven by poly-ADP-ribose polymerases (PARPs) and that the insoluble protein species arise from intrinsically disordered proteins associating with PAR-associated genomic sites in ATM-deficient cells. The lesions implicated in this process are single-strand DNA breaks dependent on reactive oxygen species, transcription, and R-loops. Human cells expressing Mre11 A-T-like disorder mutants also show PARP-dependent aggregation identical to ATM deficiency. Lastly, analysis of A-T patient cerebellum samples shows widespread protein aggregation as well as loss of proteins known to be critical in human spinocerebellar ataxias that is not observed in neocortex tissues. These results provide a hypothesis accounting for loss of protein integrity and cerebellum function in A-T.
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