ArticleNucleic acids research2012
Flap endonucleases pass 5'-flaps through a flexible arch using a disorder-thread-order mechanism to confer specificity for free 5'-ends.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
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Who cites it
35 citing papers in PubMed, 44 citations in OpenAlex.
- Functional roles for FEN1 phosphate steering residues in multi-step substrate verification prior to reaction.The Journal of biological chemistry · 2026Article
- DNA polymerase I: structure, activity, and function in bacterial DNA replication and repair.Critical reviews in biochemistry and molecular biology · 2026Review
- Decoding Cancer Variants of Unknown Significance for Helicase-Nuclease-RPA Complexes Orchestrating DNA Repair During Transcription and Replication.Frontiers in molecular biosciences · 2021Article
- Implementing fluorescence enhancement, quenching, and FRET for investigating flap endonuclease 1 enzymatic reaction at the single-molecule level.Computational and structural biotechnology journal · 2021Review
- The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair.Nucleic acids research · 2020Article
- Human XPG nuclease structure, assembly, and activities with insights for neurodegeneration and cancer from pathogenic mutations.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Intrinsic Cleavage of RNA Polymerase II Adopts a Nucleobase-independent Mechanism Assisted by Transcript Phosphate.Nature catalysis · 2019Article
- Two symmetric arginine residues play distinct roles inProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Structural basis of 5' flap recognition and protein-protein interactions of human flap endonuclease 1.Nucleic acids research · 2018Article
- A conserved loop-wedge motif moderates reaction site search and recognition by FEN1.Nucleic acids research · 2018Article
- Regional conformational flexibility couples substrate specificity and scissile phosphate diester selectivity in human flap endonuclease 1.Nucleic acids research · 2018Article
- Crystal structure and mutational analysis of Mycobacterium smegmatis FenA highlight active site amino acids and three metal ions essential for flap endonuclease and 5' exonuclease activities.Nucleic acids research · 2018Article
- Missed cleavage opportunities by FEN1 lead to Okazaki fragment maturation via the long-flap pathway.Nucleic acids research · 2018Article
- Positioning the 5'-flap junction in the active site controls the rate of flap endonuclease-1-catalyzed DNA cleavage.The Journal of biological chemistry · 2018Article
- The DNA Repair Repertoire of Mycobacterium smegmatis FenA Includes the Incision of DNA 5' Flaps and the Removal of 5' Adenylylated Products of Aborted Nick Ligation.Journal of bacteriology · 2017Article
- Comprehensive classification of the PIN domain-like superfamily.Nucleic acids research · 2017Article
- Phosphate steering by Flap Endonuclease 1 promotes 5'-flap specificity and incision to prevent genome instability.Nature communications · 2017Article
- Interplay of catalysis, fidelity, threading, and processivity in the exo- and endonucleolytic reactions of human exonuclease I.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Single-molecule FRET unveils induced-fit mechanism for substrate selectivity in flap endonuclease 1.eLife · 2017Article
- Cellularly active N-hydroxyurea FEN1 inhibitors block substrate entry to the active site.Nature chemical biology · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Flap endonucleases (FENs), essential for DNA replication and repair, recognize and remove RNA or DNA 5'-flaps. Related to FEN specificity for substrates with free 5'-ends, but controversial, is the role of the helical arch observed in varying conformations in substrate-free FEN structures. Conflicting models suggest either 5'-flaps thread through the arch, which when structured can only accommodate single-stranded (ss) DNA, or the arch acts as a clamp. Here we show that free 5'-termini are selected using a disorder-thread-order mechanism. Adding short duplexes to 5'-flaps or 3'-streptavidin does not markedly impair the FEN reaction. In contrast, reactions of 5'-streptavidin substrates are drastically slowed. However, when added to premixed FEN and 5'-biotinylated substrate, streptavidin is not inhibitory and complexes persist after challenge with unlabelled competitor substrate, regardless of flap length or the presence of a short duplex. Cross-linked flap duplexes that cannot thread through the structured arch react at modestly reduced rate, ruling out mechanisms involving resolution of secondary structure. Combined results explain how FEN avoids cutting template DNA between Okazaki fragments and link local FEN folding to catalysis and specificity: the arch is disordered when flaps are threaded to confer specificity for free 5'-ends, with subsequent ordering of the arch to catalyze hydrolysis.
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Registered trials
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