ArticleProceedings of the National Academy of Sciences of the United States of America2014
Sequential switching of binding partners on PCNA during in vitro Okazaki fragment maturation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- USP1 inhibition promotes RAD18-dependent PCNA degradation and BRCA1 synthetic lethality.bioRxiv : the preprint server for biology · 2026Article
- PARP1-mediated 5' flap dynamics facilitate Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2026Article
- Article
- Article
- 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
- Functional asymmetry in processivity clamp proteins.Biophysical journal · 2025Review
- Redundant but essential functions of PARP1 and PARP2 in DNA ligase I-independent DNA replication.Nucleic acids research · 2024Article
- Single-molecule characterization of SV40 replisome and novel factors: human FPC and Mcm10.Nucleic acids research · 2024Article
- The mRNA and microRNA Landscape of the Blastema Niche in Regenerating Newt Limbs.International journal of molecular sciences · 2024Article
- ATAD5 functions as a regulatory platform for Ub-PCNA deubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Saccharomyces cerevisiae DNA polymerase IV overcomes Rad51 inhibition of DNA polymerase δ in Rad52-mediated direct-repeat recombination.Nucleic acids research · 2023Article
- CAF-1 deposits newly synthesized histones during DNA replication using distinct mechanisms on the leading and lagging strands.Nucleic acids research · 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
- Effects of Defective Unloading and Recycling of PCNA Revealed by the Analysis ofInternational journal of molecular sciences · 2023Article
- 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
- Structure-specific nucleases: role in Okazaki fragment maturation.Trends in genetics : TIG · 2022Article
- Dynamic DNA-bound PCNA complexes co-ordinate Okazaki fragment synthesis, processing and ligation.Journal of molecular biology · 2020Article
- Structure of eukaryotic DNA polymerase δ bound to the PCNA clamp while encircling DNA.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A hand-off of DNA between archaeal polymerases allows high-fidelity replication to resume at a discrete intermediate three bases past 8-oxoguanine.Nucleic acids research · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The homotrimeric sliding clamp proliferating cell nuclear antigen (PCNA) mediates Okazaki fragment maturation through tight coordination of the activities of DNA polymerase δ (Pol δ), flap endonuclease 1 (FEN1) and DNA ligase I (Lig1). Little is known regarding the mechanism of partner switching on PCNA and the involvement of PCNA's three binding sites in coordinating such processes. To shed new light on PCNA-mediated Okazaki fragment maturation, we developed a novel approach for the generation of PCNA heterotrimers containing one or two mutant monomers that are unable to bind and stimulate partners. These heterotrimers maintain the native oligomeric structure of PCNA and exhibit high stability under various conditions. Unexpectedly, we found that PCNA heterotrimers containing only one functional binding site enable Okazaki fragment maturation by efficiently coordinating the activities of Pol δ, FEN1, and Lig1. The efficiency of switching between partners on PCNA was not significantly impaired by limiting the number of available binding sites on the PCNA ring. Our results provide the first direct evidence, to our knowledge, that simultaneous binding of multiple partners to PCNA is unnecessary, and if it occurs, does not provide significant functional advantages for PCNA-mediated Okazaki fragment maturation in vitro. In contrast to the "toolbelt" model, which was demonstrated for bacterial and archaeal sliding clamps, our results suggest a mechanism of sequential switching of partners on the eukaryotic PCNA trimer during DNA replication and repair.
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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.