ArticleProceedings of the National Academy of Sciences of the United States of America2010
Reconstitution of RPA-covered single-stranded DNA-activated ATR-Chk1 signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 142 citations in OpenAlex.
- Fission yeast RPA-TERT-Tpz1TPP1 complex promotes telomere extension and suppresses telomere recombination.PLoS genetics · 2026Article
- Twisting the End Game: How Telomere Chromatin Modifications Shape Telomere Maintenance.Aging cell · 2026Review
- RAD51C breast cancer-identified variants with attenuated homologous recombination function exhibit sensitivity to combined PARP1 and ATR inhibition.NAR cancer · 2026Article
- Fission yeast RPA-TERT-Tpz1bioRxiv : the preprint server for biology · 2026Article
- Dpb11 facilitates the colocalization of Mec1-Ddc2 with its activators on gapped DNA.Cell reports · 2026Article
- Conditional deletion of human STN1 leads to telomere dysfunction, genome instability and proliferation defects.Journal of cell science · 2026Article
- Bi-allelic WDHD1 variants cause microcephalic primordial dwarfism.American journal of human genetics · 2026Article
- Oncometabolite fumarate impairs ATR-CHK1 signaling by succinating RPA1 in fumarate hydratase-deficient renal cell carcinoma cells.Cancer & metabolism · 2026Article
- Topoisomerase I inhibitor antibody-drug conjugates in breast cancer: the relevance of the DNA damage response to resistance, response, and combination treatment strategies.Breast cancer research and treatment · 2026Review
- Article
- The RPA-binding domain and the KKRK motif in Rad26ATRIP cooperate at the perturbed DNA replication fork for initiating checkpoint signalling.PLoS genetics · 2026Article
- E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.Frontiers in oncology · 2026Review
- Molecular interplay between the DNA damage checkpoint kinase Mec1-Ddc2 and its activator Dpb11 on gapped DNA.bioRxiv : the preprint server for biology · 2025Article
- CHK1 inhibition increases the therapeutic response to radiotherapy via antitumor immunity in ARID1A-deficient colorectal cancer.Cell death & disease · 2025Article
- DNA Damage and Replication Stress Checkpoints.Annual review of biochemistry · 2025Review
- Phospho-TRIM21 orchestrates RPA2 ubiquitination switch to promote homologous recombination and tumor radio/chemo-resistance.Oncogene · 2025Article
- Targeting DNA damage sensors for cancer therapy.DNA repair · 2025Review
- Article
- Human hnRNPA1 reorganizes telomere-bound replication protein A.Nucleic acids research · 2024Article
- The effect of replication protein A inhibition and post-translational modification on ATR kinase signaling.Scientific reports · 2024Article
41 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 1 country.
Funding
Abstract
ATR kinase is a critical upstream regulator of the checkpoint response to various forms of DNA damage. Previous studies have shown that ATR is recruited via its binding partner ATR-interacting protein (ATRIP) to replication protein A (RPA)-covered single-stranded DNA (RPA-ssDNA) generated at sites of DNA damage where ATR is then activated by TopBP1 to phosphorylate downstream targets including the Chk1 signal transducing kinase. However, this critical feature of the human ATR-initiated DNA damage checkpoint signaling has not been demonstrated in a defined system. Here we describe an in vitro checkpoint system in which RPA-ssDNA and TopBP1 are essential for phosphorylation of Chk1 by the purified ATR-ATRIP complex. Checkpoint defective RPA mutants fail to activate ATR kinase in this system, supporting the conclusion that this system is a faithful representation of the in vivo reaction. Interestingly, we find that an alternative form of RPA (aRPA), which does not support DNA replication, can substitute for the checkpoint function of RPA in vitro, thus revealing a potential role for aRPA in the activation of ATR kinase. We also find that TopBP1 is recruited to RPA-ssDNA in a manner dependent on ATRIP and that the N terminus of TopBP1 is required for efficient recruitment and activation of ATR kinase.
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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.