ArticleNucleic acids research2008
PCNA stimulates catalysis by structure-specific nucleases using two distinct mechanisms: substrate targeting and catalytic step.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
12 citing papers in PubMed, 32 citations in OpenAlex.
- Mechanism of PCNA loading by Ctf18-RFC for leading-strand DNA synthesis.Science (New York, N.Y.) · 2024Article
- Activation of the mismatch-specific endonuclease EndoMS/NucS by the replication clamp is required for high fidelity DNA replication.Nucleic acids research · 2018Article
- Role of PCNA and RFC in promoting Mus81-complex activity.BMC biology · 2017Article
- Proliferating cell nuclear antigen restores the enzymatic activity of a DNA ligase I deficient in DNA binding.FEBS open bio · 2017Article
- Article
- Single-molecule characterization of Fen1 and Fen1/PCNA complexes acting on flap substrates.Nucleic acids research · 2014Article
- Characterization of the human SNM1A and SNM1B/Apollo DNA repair exonucleases.The Journal of biological chemistry · 2012Article
- Modulation of the Pyrococcus abyssi NucS endonuclease activity by replication clamp at functional and structural levels.The Journal of biological chemistry · 2012Article
- Coordination of multiple enzyme activities by a single PCNA in archaeal Okazaki fragment maturation.The EMBO journal · 2012Article
- Staphylococcus aureus DinG, a helicase that has evolved into a nuclease.The Biochemical journal · 2012Article
- Mec1/Tel1-dependent phosphorylation of Slx4 stimulates Rad1-Rad10-dependent cleavage of non-homologous DNA tails.DNA repair · 2010Article
- PCNA and XPF cooperate to distort DNA substrates.Nucleic acids research · 2010Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The sliding clamp Proliferating Cell Nuclear Antigen (PCNA) functions as a recruiter and organizer of a wide variety of DNA modifying enzymes including nucleases, helicases, polymerases and glycosylases. The 5'-flap endonuclease Fen-1 is essential for Okazaki fragment processing in eukaryotes and archaea, and is targeted to the replication fork by PCNA. Crenarchaeal XPF, a 3'-flap endonuclease, is also stimulated by PCNA in vitro. Using a novel continuous fluorimetric assay, we demonstrate that PCNA activates these two nucleases by fundamentally different mechanisms. PCNA stimulates Fen-1 by increasing the enzyme's binding affinity for substrates, as suggested previously. However, PCNA activates XPF by increasing the catalytic rate constant by four orders of magnitude without affecting the K(M). PCNA may function as a platform upon which XPF exerts force to distort DNA substrates, destabilizing the substrate and/or stabilizing the transition state structure. This suggests that PCNA can function directly in supporting catalysis as an essential cofactor in some circumstances, a new role for a protein that is generally assumed to perform a passive targeting and organizing function in molecular biology. This could provide a mechanism for the exquisite control of nuclease activity targeted to specific circumstances, such as replication forks or damaged DNA with pre-loaded PCNA.
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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.