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Expanding the repertoire of DNA polymerase substrates: template-instructed incorporation of non-nucleoside triphosphate analogues by DNA polymerases β and λ

Crespan, Emmanuele ; Alexandrova, Ludmila ; Khandazhinskaya, Anastasiya ; Jasko, Maxim ; Kukhanova, Marina ; Villani, Giuseppe ; Hübscher, Ulrich ; Spadari, Silvio ; Maga, Giovanni

In: Nucleic Acids Research, 2006, vol. 35, no. 1, p. 45-57

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    Titre
    • Expanding the repertoire of DNA polymerase substrates: template-instructed incorporation of non-nucleoside triphosphate analogues by DNA polymerases β and λ
    Auteur
    • Crespan, Emmanuele. Istituto di Genetica Molecolare, IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy, 32 Vavilov Street, 119991 Moscow, Russia, 205 route de Narbonne, 31077 Toulouse Cedex, France, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
    • Alexandrova, Ludmila. Engelhardt Institute of Molecular Biology, RAS 32 Vavilov Street, 119991 Moscow, Russia
    • Khandazhinskaya, Anastasiya. Engelhardt Institute of Molecular Biology, RAS 32 Vavilov Street, 119991 Moscow, Russia
    • Jasko, Maxim. Engelhardt Institute of Molecular Biology, RAS 32 Vavilov Street, 119991 Moscow, Russia
    • Kukhanova, Marina. Engelhardt Institute of Molecular Biology, RAS 32 Vavilov Street, 119991 Moscow, Russia
    • Villani, Giuseppe. Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique 205 route de Narbonne, 31077 Toulouse Cedex, France
    • Hübscher, Ulrich. Institute of Veterinary Biochemistry and Molecular Biology University of Zürich-Irchel Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
    • Spadari, Silvio. Istituto di Genetica Molecolare, IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy, 32 Vavilov Street, 119991 Moscow, Russia, 205 route de Narbonne, 31077 Toulouse Cedex, France, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
    • Maga, Giovanni. Istituto di Genetica Molecolare, IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy, 32 Vavilov Street, 119991 Moscow, Russia, 205 route de Narbonne, 31077 Toulouse Cedex, France, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Nucleic Acids Research, 2006, vol. 35, no. 1, p. 45-57. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:303292
    Summary
    We have recently shown that neither the base nor the sugar moieties of a nucleotide is an essential feature for its incorporation by DNA polymerases (pols) λ and β. Here we present the identification of novel non-nucleoside triphosphate (NNTP) derivatives belonging to three classes: (i) non-substrate-specific inhibitors of DNA pol λ; (ii) substrate inhibitors which could preferentially be incorporated by either DNA pol λ wild type or its Y505A mutant and (iii) the substrate inhibitor N-(Biphenylcarbonyl)-4-oxobutyl triphosphate which could be incorporated exclusively by DNA pol β in a Mg2+-dependent manner, and preferentially pairs with A on the template. This compound represents the first example of a substrate lacking both nucleobase and ribose residue, showing distinct base-pairing properties with normal bases. Therefore, this NNTP analog can be considered as the prototype of an entirely novel class of DNA pol substrates