ArticleNucleic acids research2016
Cooperative motion of a key positively charged residue and metal ions for DNA replication catalyzed by human DNA Polymerase-η.
Article in Nucleic acids research, 2016. 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, 42 citations in OpenAlex.
- Coordinated Residue Motions at the Enzyme-Substrate Interface Promote DNA Translocation in Polymerases.Journal of the American Chemical Society · 2025Article
- Effects of the Y432S Cancer-Associated Variant on the Reaction Mechanism of Human DNA Polymerase κ.Journal of chemical information and modeling · 2024Article
- Controlled sulfur-based engineering confers mouldability to phosphorothioate antisense oligonucleotides.Nucleic acids research · 2023Article
- Article
- A metal ion-dependent conformational switch modulates activity of the Plasmodium M17 aminopeptidase.The Journal of biological chemistry · 2022Article
- Mechanism of reaction of RNA-dependent RNA polymerase from SARS-CoV-2.Chem catalysis · 2022Article
- Controlled Trafficking of Multiple and Diverse Cations Prompts Nucleic Acid Hydrolysis.ACS catalysis · 2021Article
- Recruiting Mechanism and Functional Role of a Third Metal Ion in the Enzymatic Activity of 5' Structure-Specific Nucleases.Journal of the American Chemical Society · 2020Article
- A synthetic genetic polymer with an uncharged backbone chemistry based on alkyl phosphonate nucleic acids.Nature chemistry · 2019Article
- Dynamic coordination of two-metal-ions orchestrates λ-exonuclease catalysis.Nature communications · 2018Article
- Exploring the Role of the Third Active Site Metal Ion in DNA Polymerase η with QM/MM Free Energy Simulations.Journal of the American Chemical Society · 2018Article
- Pyrophosphate hydrolysis is an intrinsic and critical step of the DNA synthesis reaction.Nucleic acids research · 2018Article
- Second-Shell Basic Residues Expand the Two-Metal-Ion Architecture of DNA and RNA Processing Enzymes.Structure (London, England : 1993) · 2018Article
- Pyrophosphate Release in the Protein HIV Reverse Transcriptase.The journal of physical chemistry. B · 2017Article
- Time-lapse crystallography snapshots of a double-strand break repair polymerase in action.Nature communications · 2017Article
- Effects of Active Site Mutations on Specificity of Nucleobase Binding in Human DNA Polymerase η.The journal of physical chemistry. B · 2017Article
- Advances in Structural and Single-Molecule Methods for Investigating DNA Lesion Bypass and Repair Polymerases.Chemical research in toxicology · 2017Article
- Rate-limiting Pyrophosphate Release by HIV Reverse Transcriptase Improves Fidelity.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trans-lesion synthesis polymerases, like DNA Polymerase-η (Pol-η), are essential for cell survival. Pol-η bypasses ultraviolet-induced DNA damages via a two-metal-ion mechanism that assures DNA strand elongation, with formation of the leaving group pyrophosphate (PPi). Recent structural and kinetics studies have shown that Pol-η function depends on the highly flexible and conserved Arg61 and, intriguingly, on a transient third ion resolved at the catalytic site, as lately observed in other nucleic acid-processing metalloenzymes. How these conserved structural features facilitate DNA replication, however, is still poorly understood. Through extended molecular dynamics and free energy simulations, we unravel a highly cooperative and dynamic mechanism for DNA elongation and repair, which is here described by an equilibrium ensemble of structures that connect the reactants to the products in Pol-η catalysis. We reveal that specific conformations of Arg61 help facilitate the recruitment of the incoming base and favor the proper formation of a pre-reactive complex in Pol-η for efficient DNA editing. Also, we show that a third transient metal ion, which acts concertedly with Arg61, serves as an exit shuttle for the leaving PPi. Finally, we discuss how this effective and cooperative mechanism for DNA repair may be shared by other DNA-repairing polymerases.
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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.