ArticleJournal of molecular biology2020
Dynamic DNA-bound PCNA complexes co-ordinate Okazaki fragment synthesis, processing and ligation.
Article in Journal of molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- PARP1-mediated 5' flap dynamics facilitate Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2026Article
- DNA extrusion size determines pathway choice during CAG repeat expansion.Nucleic acids research · 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
- Structural and molecular basis of PCNA-activated FAN1 nuclease function in DNA repair.Nature communications · 2025Article
- Joining of DNA breaks- interplay between DNA ligases and poly (ADP-ribose) polymerases.DNA repair · 2025Review
- CDK-dependent phosphorylation regulates PNKP function in DNA replication.The Journal of biological chemistry · 2024Article
- Redundant but essential functions of PARP1 and PARP2 in DNA ligase I-independent DNA replication.Nucleic acids research · 2024Article
- Review
- Mammalian DNA ligases; roles in maintaining genome integrity.Journal of molecular biology · 2024Review
- The Atad5 RFC-like complex is the major unloader of proliferating cell nuclear antigen in Xenopus egg extracts.The Journal of biological chemistry · 2024Article
- A four-point molecular handover during Okazaki maturation.Nature structural & molecular biology · 2023Article
- Molecular insight into the PCNA-binding mode of FBH1.Structure (London, England : 1993) · 2023Article
- Unchanged PCNA and DNMT1 dynamics during replication in DNA ligase I-deficient cells but abnormal chromatin levels of non-replicative histone H1.Scientific reports · 2023Article
- Mechanistic investigation of human maturation of Okazaki fragments reveals slow kinetics.Nature communications · 2022Article
- Review
- Rad53 arrests leading and lagging strand DNA synthesis via distinct mechanisms in response to DNA replication stress.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Cryo-EM structures and biochemical insights into heterotrimeric PCNA regulation of DNA ligase.Structure (London, England : 1993) · 2022Article
- Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis.Open medicine (Warsaw, Poland) · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
More than a million Okazaki fragments are synthesized, processed and joined during replication of the human genome. After synthesis of an RNA-DNA oligonucleotide by DNA polymerase α holoenzyme, proliferating cell nuclear antigen (PCNA), a homotrimeric DNA sliding clamp and polymerase processivity factor, is loaded onto the primer-template junction by replication factor C (RFC). Although PCNA interacts with the enzymes DNA polymerase δ (Pol δ), flap endonuclease 1 (FEN1) and DNA ligase I (LigI) that complete Okazaki fragment processing and joining, it is not known how the activities of these enzymes are coordinated. Here we describe a novel interaction between Pol δ and LigI that is critical for Okazaki fragment joining in vitro. Both LigI and FEN1 associate with PCNA-Pol δ during gap-filling synthesis, suggesting that gap-filling synthesis is carried out by a complex of PCNA, Pol δ, FEN1 and LigI. Following ligation, PCNA and LigI remain on the DNA, indicating that Pol δ and FEN1 dissociate during 5' end processing and that LigI engages PCNA at the DNA nick generated by FEN1 and Pol δ. Thus, dynamic PCNA complexes coordinate Okazaki fragment synthesis and processing with PCNA and LigI forming a terminal structure of two linked protein rings encircling the ligated DNA.
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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.