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Analysis of institutional authors

Lázaro J.m.AuthorSalas M.Author

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June 2, 2024
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Article
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Kinetic mechanisms governing stable ribonucleotide incorporation in individual DNA polymerase complexes

Publicated to: BIOCHEMISTRY. 53 (51): 8061-8076 - 2014-01-01 53(51), DOI: 10.1021/bi501216a

Authors:

Dahl JM; Wang H; Lázaro JM; Salas M; Lieberman KR
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Affiliations

Department of Applied Mathematics and Statistics; Baskin School of Engineering; University of California; Santa Cruz; 95064; CA; United States - Author
Department of Biomolecular Engineering; Baskin School of Engineering; University of California; Santa Cruz; 95064; CA; United States - Author
Department of Computer Engineering; Baskin School of Engineering; University of California; Santa Cruz; 95064; CA; United States; Instituto de Biología Molecular Eladio Viñuela (CSIC); Centro de Biología Molecular Severo Ochoa (CSIC-UAM); Universidad Autó - Author
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Abstract

Ribonucleoside triphosphates (rNTPs) are frequently incorporated during DNA synthesis by replicative DNA polymerases (DNAPs), and once incorporated are not efficiently edited by the DNAP exonucleolytic function. We examined the kinetic mechanisms that govern selection of complementary deoxyribonucleoside triphosphates (dNTPs) over complementary rNTPs and that govern the probability of a complementary ribonucleotide at the primer terminus escaping exonucleolytic editing and becoming stably incorporated. We studied the quantitative responses of individual Φ29 DNAP complexes to ribonucleotides using a kinetic framework, based on our prior work, in which transfer of the primer strand from the polymerase to exonuclease site occurs prior to translocation, and translocation precedes dNTP binding. We determined transition rates between the pre-translocation and post-translocation states, between the polymerase and exonuclease sites, and for dNTP or rNTP binding, with single-nucleotide spatial precision and submillisecond temporal resolution, from ionic current time traces recorded when individual DNAP complexes are held atop a nanopore in an electric field. The predominant response to the presence of a ribonucleotide in Φ29 DNAP complexes before and after covalent incorporation is significant destabilization, relative to the presence of a deoxyribonucleotide. This destabilization is manifested in the post-translocation state prior to incorporation as a substantially higher rNTP dissociation rate and manifested in the pre-translocation state after incorporation as rate increases for both primer strand transfer to the exonuclease site and the forward translocation, with the probability of editing not directly increased. In the post-translocation state, the primer terminal 2′-OH group also destabilizes dNTP binding. (Figure Presented). © 2014 American Chemical Society.
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Keywords

ArticleBacillus phageBacillus phagesBinding sitesBiological modelChemical structureChemistryCrystal structureDeoxyribonucleoside triphosphateDeoxyribonucleotideDeoxyribonucleotidesDissociationDissociation ratesDnaDna directed dna polymeraseDna polymeraseDna primersDna protein complexDna replicationDna-directed dna polymeraseElectric fieldsEnzyme bindingEnzyme structureEnzymologyExonucleaseGeneticsIon currentKinetic mechanismKineticsMetabolismModels, biologicalModels, molecularMutagenesis, site-directedNanoporeNanoporesPolymersPrimer dnaPrimer terminusRecombinant proteinRecombinant proteinsRibonucleosidesRibonucleotideRibonucleotidesSingle nucleotidesSite directed mutagenesisTemporal resolutionTransition ratesViral proteinsVirus protein

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal BIOCHEMISTRY due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2014, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-01-02:

  • Scopus: 6
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-01-02:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 29.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 29 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United States of America.

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