ArticleScience advances2022
CHK1 phosphorylates PRIMPOL to promote replication stress tolerance.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
- An updated view on lagging strand DNA replication: implications for the replication stress response.Cell cycle (Georgetown, Tex.) · 2026Article
- Targeting common denominators of DNA damage tolerance mechanisms as therapeutic strategy to cope with dynamic phenotypic changes in triple-negative breast cancer cells.Cell death discovery · 2026Article
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- The polymerase milieu of human papillomavirus.Journal of virology · 2026Review
- G-quadruplex homeostasis is a determinant of PARP inhibitor toxicity in BRCA2-deficient cells.Nature communications · 2026Article
- SLX4IP limits replication stress globally and at ALT telomeres.The EMBO journal · 2026Article
- Lentivirus enables the detection of strand-specific ssDNA gaps by the DNA fiber spreading assay.Communications biology · 2026Article
- Topological stress regulates replication fork dynamics in unperturbed S phase.Nature communications · 2026Article
- The DNA helicase HELQ promotes replication fork reversal in coordination with BRCA2- and FANCD2-mediated repair pathways.Nucleic acids research · 2026Article
- BE screen reveals METTL3 S2 dephosphorylation sensitizes gastric cancer cells to oxaliplatin by interfering METTL3-eIF3H interaction.Science advances · 2025Article
- SLFN11 counteracts the RFWD3-PRIMPOL DNA damage tolerance axis to restrain gapped DNA synthesis in response to replication stress.Nature communications · 2025Article
- The need for speed: drivers and consequences of accelerated replication forks.Communications biology · 2025Review
- Eukaryotic Lagging Strand Synthesis is Distributive.bioRxiv : the preprint server for biology · 2025Article
- Mouse PrimPol Outperforms Its Human Counterpart as a Robust DNA Primase.International journal of molecular sciences · 2025Article
- S-phase checkpoint protects from aberrant replication fork processing and degradation.Nucleic acids research · 2025Article
- DNA polymerase α/primase extraction from chromatin by VCP/p97 restricts ATR activation during unperturbed DNA replication.Nature communications · 2025Article
- The DNA-PKcs/JNK/p53 pathway underlies changes in cell fate decision toward death during DNA replication catastrophe.Nucleic acids research · 2025Article
- Replication stress responses in human lymphocytes change sex-specifically during aging.Nucleic acids research · 2025Article
- Review
- PARP inhibition-associated heterochromatin confers increased DNA replication stress and vulnerability to ATR inhibition in SMARCA4-deficient cells.Cell death discovery · 2025Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Replication-coupled DNA repair and damage tolerance mechanisms overcome replication stress challenges and complete DNA synthesis. These pathways include fork reversal, translesion synthesis, and repriming by specialized polymerases such as PRIMPOL. Here, we investigated how these pathways are used and regulated in response to varying replication stresses. Blocking lagging-strand priming using a POLα inhibitor slows both leading- and lagging-strand synthesis due in part to RAD51-, HLTF-, and ZRANB3-mediated, but SMARCAL1-independent, fork reversal. ATR is activated, but CHK1 signaling is dampened compared to stalling both the leading and lagging strands with hydroxyurea. Increasing CHK1 activation by overexpressing CLASPIN in POLα-inhibited cells promotes replication elongation through PRIMPOL-dependent repriming. CHK1 phosphorylates PRIMPOL to promote repriming irrespective of the type of replication stress, and this phosphorylation is important for cellular resistance to DNA damage. However, PRIMPOL activation comes at the expense of single-strand gap formation, and constitutive PRIMPOL activity results in reduced cell fitness.
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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 Socratic graph.