ArticleNucleic acids research2012
Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers.
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Who cites it
157 citing papers in PubMed, 260 citations in OpenAlex.
- PARG inhibition reduces ssDNA levels and limits RPA loading upon replication fork collapse.EMBO reports · 2026Article
- Unsupervised Deep Representation Learning and Probabilistic Clustering for the Systems-Level Discovery of Germline Mutation Signatures in Pediatric Cancers.Biomedicines · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- SLX4IP limits replication stress globally and at ALT telomeres.The EMBO journal · 2026Article
- Microhomology-mediated end joining acts directly on replication forks to repair single-ended double-strand breaks.Molecular cell · 2026Article
- R-loop processing via REXO4-RNaseH1-mediated endo- and exo-cleavage coupling mode prevents genome instability and antitumor immunity.Science advances · 2026Article
- Elimusertib, a Novel ATR Inhibitor, Induces Anti-tumor Effects through Replication Catastrophe in Breast Cancers.Cancer research and treatment · 2026Article
- Mechanism of RPA phosphocode priming and tuning by CDK1/WEE1 signaling circuit.Nature communications · 2025Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Cyclin D1 overexpression induces replication stress and microhomology-mediated end-joining dependence in mantle cell lymphoma.The Journal of clinical investigation · 2025Article
- Adeno-Associated Virus 2 (AAV2) - Induced RPA exhaustion generates cellular DNA damage and restricts viral gene expression.PLoS pathogens · 2025Article
- The DNA-PKcs/JNK/p53 pathway underlies changes in cell fate decision toward death during DNA replication catastrophe.Nucleic acids research · 2025Article
- SLX4IP acts in parallel to FANCM to limit BLM-dependent replication stress at ALT telomeres.bioRxiv : the preprint server for biology · 2025Article
- Targeting DNA damage sensors for cancer therapy.DNA repair · 2025Review
- Myristoylated Eepd1 Enhances Lipolysis and Thermogenesis through PKA Activation to Combat Obesity.Nature communications · 2025Article
- O-GlcNAcylation of RPA2 at S4/S8 antagonizes phosphorylation and regulates checkpoint activation during replication stress.The Journal of biological chemistry · 2024Article
- p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis.Nucleic acids research · 2024Article
- DNA damage-induced phosphorylation of a replicative DNA helicase results in inhibition of DNA replication through attenuation of helicase function.Nucleic acids research · 2024Article
- Intrinsic PARG inhibitor sensitivity is mimicked byNAR cancer · 2024Article
- The effect of replication protein A inhibition and post-translational modification on ATR kinase signaling.Scientific reports · 2024Article
97 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
DNA damage encountered by DNA replication forks poses risks of genome destabilization, a precursor to carcinogenesis. Damage checkpoint systems cause cell cycle arrest, promote repair and induce programed cell death when damage is severe. Checkpoints are critical parts of the DNA damage response network that act to suppress cancer. DNA damage and perturbation of replication machinery causes replication stress, characterized by accumulation of single-stranded DNA bound by replication protein A (RPA), which triggers activation of ataxia telangiectasia and Rad3 related (ATR) and phosphorylation of the RPA32, subunit of RPA, leading to Chk1 activation and arrest. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) [a kinase related to ataxia telangiectasia mutated (ATM) and ATR] has well characterized roles in DNA double-strand break repair, but poorly understood roles in replication stress-induced RPA phosphorylation. We show that DNA-PKcs mutant cells fail to arrest replication following stress, and mutations in RPA32 phosphorylation sites targeted by DNA-PKcs increase the proportion of cells in mitosis, impair ATR signaling to Chk1 and confer a G2/M arrest defect. Inhibition of ATR and DNA-PK (but not ATM), mimic the defects observed in cells expressing mutant RPA32. Cells expressing mutant RPA32 or DNA-PKcs show sustained H2AX phosphorylation in response to replication stress that persists in cells entering mitosis, indicating inappropriate mitotic entry with unrepaired damage.
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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.