ArticleGenes & development2005
Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint.
Article in Genes & development, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 471 papers.
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Who cites it
471 citing papers in PubMed, 750 citations in OpenAlex.
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- Antibiotic-Induced Genotoxicity: Molecular Mechanisms, Cytogenetic Damage, and Implications for Human Health.International journal of molecular sciences · 2026Review
- PARG inhibition reduces ssDNA levels and limits RPA loading upon replication fork collapse.EMBO reports · 2026Article
- Structural mechanism of TOPBP1 activating the ATR-ATRIP replication checkpoint kinase.Nature structural & molecular biology · 2026Article
- Replication stress induced exposure to methotrexate in root meristem cells of Vicia faba.Histochemistry and cell biology · 2026Article
- SLX4IP limits replication stress globally and at ALT telomeres.The EMBO journal · 2026Article
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- LIPT1 loss confers replication stress and PARP inhibitor sensitivity through PrimPol-mediated ssDNA gaps.Science advances · 2026Article
- The DNA helicase HELQ promotes replication fork reversal in coordination with BRCA2- and FANCD2-mediated repair pathways.Nucleic acids research · 2026Article
- Phytochemical-Based Strategies for Lung Cancer: Clinical Insights Into Pleiotropic Molecular Signaling and Therapeutic Roles.Phytotherapy research : PTR · 2026Review
- β-tubulin phosphorylation by Chk1 is required for normal spindle formation during cell division.Communications biology · 2026Article
- Cellular Senescence Triggered by Food and Environmental Genotoxins.International journal of molecular sciences · 2026Review
- Cryo-electron microscopic visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2.Science (New York, N.Y.) · 2026Article
- Overexpression of CDT1 inhibits cell cycle progression at S phase by interacting with the mini-chromosome maintenance complex and causes DNA damage.FEBS open bio · 2026Article
- Parental Histone Recycling During Chromatin Replication.Biomolecules · 2025Review
- NUFIP1 at the crossroads of ribophagy and disease: unveiling therapeutic implications.Journal of translational medicine · 2025Review
- Decoding replication stress responses through post-translational modifications.Nature chemical biology · 2025Review
411 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The ATR-dependent DNA damage response pathway can respond to a diverse group of lesions as well as inhibitors of DNA replication. Using the Xenopus egg extract system, we show that lesions induced by UV irradiation and cis-platinum cause the functional uncoupling of MCM helicase and DNA polymerase activities, an event previously shown for aphidicolin. Inhibition of uncoupling during elongation with inhibitors of MCM7 or Cdc45, a putative helicase cofactor, results in abrogation of Chk1 phosphorylation, indicating that uncoupling is necessary for activation of the checkpoint. However, uncoupling is not sufficient for checkpoint activation, and DNA synthesis by Polalpha is also required. Finally, using plasmids of varying size, we demonstrate that all of the unwound DNA generated at a stalled replication fork can contribute to the level of Chk1 phosphorylation, suggesting that uncoupling amplifies checkpoint signaling at each individual replication fork. Taken together, these observations indicate that functional uncoupling of MCM helicase and DNA polymerase activities occurs in response to multiple forms of DNA damage and that there is a general mechanism for generation of the checkpoint-activating signal following DNA damage.
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What OpenQuestion holds
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.