ArticleMolecular cell2018
The Importance of Poly(ADP-Ribose) Polymerase as a Sensor of Unligated Okazaki Fragments during DNA Replication.
Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 263 papers.
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Who cites it
263 citing papers in PubMed, 394 citations in OpenAlex.
- The Fanconi anemia pathway restrains MLL-rearranged leukemogenesis through suppressing non-homologous end joining-mediated genomic instability.Nature communications · 2026Article
- FANCA-dependent FEN1 recruitment suppresses transcription-replication conflicts and PARPi sensitivity.Molecular cell · 2026Article
- PARG inhibition reduces ssDNA levels and limits RPA loading upon replication fork collapse.EMBO reports · 2026Article
- LIG1 Loss in TP53-mutant Triple Negative Breast Cancer Rewires DNA Repair and Confers Sensitivity to PARP-ATR Inhibitor Combinations.Molecular cancer therapeutics · 2026Article
- FET proteins and PARylation-dependent condensates promote replication fork reversal and genome stability.Nature communications · 2026Article
- CHD1L maintains genome integrity by facilitating okazaki fragment maturation.Nucleic acids research · 2026Article
- NovelNeurology. Genetics · 2026Article
- SLX4IP limits replication stress globally and at ALT telomeres.The EMBO journal · 2026Article
- Distinct repair outcomes from single and convergent replication fork collapse.Nature structural & molecular biology · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- Lentivirus enables the detection of strand-specific ssDNA gaps by the DNA fiber spreading assay.Communications biology · 2026Article
- PARP1-mediated 5' flap dynamics facilitate Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2026Article
- Replication protein A protects lagging strand gaps, restricting PARP inhibitor-induced synthetic lethality in BRCA1-deficient tumors.Nucleic acids research · 2026Article
- Understanding single stranded DNA gaps: from formation to fate.The Biochemical journal · 2026Review
- Versatile and sensitive detection of mono- and poly(ADP-ribosyl)ation reveals XRCC1-dependent remodelling of PARP1 signalling.Nature communications · 2026Article
- Mutant p53 Directs PARP to Regulate Replication Stress and Drive Breast Cancer Metastasis.bioRxiv : the preprint server for biology · 2026Article
- Cancer-associated TRF1 mutations alter PARP1 interaction dynamics: an in silico study.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
203 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Poly(ADP-ribose) is synthesized by PARP enzymes during the repair of stochastic DNA breaks. Surprisingly, however, we show that most if not all endogenous poly(ADP-ribose) is detected in normal S phase cells at sites of DNA replication. This S phase poly(ADP-ribose) does not result from damaged or misincorporated nucleotides or from DNA replication stress. Rather, perturbation of the DNA replication proteins LIG1 or FEN1 increases S phase poly(ADP-ribose) more than 10-fold, implicating unligated Okazaki fragments as the source of S phase PARP activity. Indeed, S phase PARP activity is ablated by suppressing Okazaki fragment formation with emetine, a DNA replication inhibitor that selectively inhibits lagging strand synthesis. Importantly, PARP activation during DNA replication recruits the single-strand break repair protein XRCC1, and human cells lacking PARP activity and/or XRCC1 are hypersensitive to FEN1 perturbation. Collectively, our data indicate that PARP1 is a sensor of unligated Okazaki fragments during DNA replication and facilitates their repair.
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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.