ArticleMolecular cell2020
PRIMPOL-Mediated Adaptive Response Suppresses Replication Fork Reversal in BRCA-Deficient Cells.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
176 citing papers in PubMed, 1 synthesis or guideline pooled it, 266 citations in OpenAlex.
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- 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
- The polymerase milieu of human papillomavirus.Journal of virology · 2026Review
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- Article
- TET2 loss triggers ssDNA gap accumulation and heightened PARP inhibitor sensitivity.Nature communications · 2026Article
- Exploiting DNA damage tolerance for precision oncology.Trends in cancer · 2026Review
- SMARCAL1 is a candidate therapeutic target for ALT-positive tumors.Genes & development · 2026Article
- The BRCA1-A complex restricts replication fork reversal-dependent DNA repair in ATM deficient cells.Nature communications · 2026Article
- 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
- 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
- DNAi: an open-source AI tool for unbiased DNA fiber analysis.Nucleic acids research · 2026Article
- Distinct mechanisms of replication stress induced by oncogenic RAS and cyclin E1 converge on R-loop-dependent fork reversal.Nature communications · 2026Article
- RF-SIRF reveals a replication stress-specific epigenetic code by spatio-temporal mapping of reversed forks.Nature communications · 2026Article
- The BRCA1-A complex restricts replication fork reversal-dependent DNA repair in ATM deficient cells.bioRxiv : the preprint server for biology · 2026Article
- The RRM domains of PARP14 mediate replication fork degradation in BRCA2-deficient cells.NAR cancer · 2026Article
116 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
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Acute treatment with replication-stalling chemotherapeutics causes reversal of replication forks. BRCA proteins protect reversed forks from nucleolytic degradation, and their loss leads to chemosensitivity. Here, we show that fork degradation is no longer detectable in BRCA1-deficient cancer cells exposed to multiple cisplatin doses, mimicking a clinical treatment regimen. This effect depends on increased expression and chromatin loading of PRIMPOL and is regulated by ATR activity. Electron microscopy and single-molecule DNA fiber analyses reveal that PRIMPOL rescues fork degradation by reinitiating DNA synthesis past DNA lesions. PRIMPOL repriming leads to accumulation of ssDNA gaps while suppressing fork reversal. We propose that cells adapt to repeated cisplatin doses by activating PRIMPOL repriming under conditions that would otherwise promote pathological reversed fork degradation. This effect is generalizable to other conditions of impaired fork reversal (e.g., SMARCAL1 loss or PARP inhibition) and suggests a new strategy to modulate cisplatin chemosensitivity by targeting the PRIMPOL pathway.
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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.