ArticleNucleic acids research2019
Processing of eukaryotic Okazaki fragments by redundant nucleases can be uncoupled from ongoing DNA replication in vivo.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- SLX4IP limits replication stress globally and at ALT telomeres.The EMBO journal · 2026Article
- Cruciform-forming AT/TA repeats are acted upon by structure-selective endonucleases and Rad51 prior to repositioning to the nuclear periphery for repair.Nucleic acids research · 2026Article
- Rad27/FEN1 prevents accumulation of Okazaki fragments and ribosomal DNA copy number changes.FEBS letters · 2025Article
- JMJD1B-mediated FEN1 demethylation allows timely switching of Okazaki fragment maturation core enzymes to avoid mutagenic flap ligation by PARP1-LIG3.bioRxiv : the preprint server for biology · 2025Article
- DNA lesions can frequently precede DNA:RNA hybrid accumulation.Nature communications · 2025Article
- Dominant and genome-wide formation of DNA:RNA hybrid G-quadruplexes in living yeast cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- High fidelity DNA ligation prevents single base insertions in the yeast genome.Nature communications · 2024Article
- Timely lagging strand maturation relies on Ubp10 deubiquitylase-mediated PCNA dissociation from replicating chromatin.Nature communications · 2024Article
- Monitoring and quantifying replication fork dynamics with high-throughput methods.Communications biology · 2024Review
- EXO1 protects BRCA1-deficient cells against toxic DNA lesions.Molecular cell · 2024Article
- ERK2-topoisomerase II regulatory axis is important for gene activation in immediate early genes.Nature communications · 2023Article
- Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis.Nucleic acids research · 2023Article
- Rothmund-Thomson syndrome, a disorder far from solved.Frontiers in aging · 2023Review
- Genome Replication Is Associated With Release of Immunogenic DNA Waste.Frontiers in immunology · 2022Article
- Post-replicative nick translation occurs on the lagging strand during prolonged depletion of DNA ligase I in Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2021Article
- HPF1-dependent PARP activation promotes LIG3-XRCC1-mediated backup pathway of Okazaki fragment ligation.Nucleic acids research · 2021Article
- Review
- Mismatch repair: Choreographing accurate strand excision.Current biology : CB · 2021Article
- Ligation of newly replicated DNA controls the timing of DNA mismatch repair.Current biology : CB · 2021Article
- Dynamic regulation of Pif1 acetylation is crucial to the maintenance of genome stability.Current genetics · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Prior to ligation, each Okazaki fragment synthesized on the lagging strand in eukaryotes must be nucleolytically processed. Nuclease cleavage takes place in the context of 5' flap structures generated via strand-displacement synthesis by DNA polymerase delta. At least three DNA nucleases: Rad27 (Fen1), Dna2 and Exo1, have been implicated in processing Okazaki fragment flaps. However, neither the contributions of individual nucleases to lagging-strand synthesis nor the structure of the DNA intermediates formed in their absence have been fully defined in vivo. By conditionally depleting lagging-strand nucleases and directly analyzing Okazaki fragments synthesized in vivo in Saccharomyces cerevisiae, we conduct a systematic evaluation of the impact of Rad27, Dna2 and Exo1 on lagging-strand synthesis. We find that Rad27 processes the majority of lagging-strand flaps, with a significant additional contribution from Exo1 but not from Dna2. When nuclease cleavage is impaired, we observe a reduction in strand-displacement synthesis as opposed to the widespread generation of long Okazaki fragment 5' flaps, as predicted by some models. Further, using cell cycle-restricted constructs, we demonstrate that both the nucleolytic processing and the ligation of Okazaki fragments can be uncoupled from DNA replication and delayed until after synthesis of the majority of the genome is complete.
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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.