Inhibition of DNA replication by an anti-PCNA aptamer/PCNA complex

Ewa Kowalska, Filip Bartnicki, Ryo Fujisawa, Piotr Bonarek, Pawet Hermanowicz, Toshiki Tsurimoto, Klaudia Muszynska, Wojciech Strzalka

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6 Citations (Scopus)

Abstract

Proliferating cell nuclear antigen (PCNA) is a multifunctional protein present in the nuclei of eukaryotic cells that plays an important role as a component of the DNA replication machinery, as well as DNA repair systems. PCNA was recently proposed as a potential non-oncogenic target for anti-cancer therapy. In this study, using the Systematic Evolution of Ligands by EXponential enrichment (SELEX) method, we developed a short DNA aptamer that binds human PCNA. In the presence of PCNA, the anti-PCNA aptamer inhibited the activity of human DNA polymerase and at nM concentrations. Moreover, PCNA protected the anti-PCNA aptamer against the exonucleolytic activity of these DNA polymerases. Investigation of the mechanism of anti-PCNA aptamer-dependent inhibition of DNA replication revealed that the aptamer did not block formation, but was a component of PCNA/DNA polymerase or complexes. Additionally, the anti-PCNA aptamer competed with the primer-template DNA for binding to the PCNA/DNA polymerase or complex. Based on the observations, a model of anti-PCNA aptamer/PCNA complex-dependent inhibition of DNA replication was proposed.

Original languageEnglish
Pages (from-to)25-41
Number of pages17
JournalNucleic acids research
Volume46
Issue number1
DOIs
Publication statusPublished - 2018

All Science Journal Classification (ASJC) codes

  • Genetics

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    Kowalska, E., Bartnicki, F., Fujisawa, R., Bonarek, P., Hermanowicz, P., Tsurimoto, T., Muszynska, K., & Strzalka, W. (2018). Inhibition of DNA replication by an anti-PCNA aptamer/PCNA complex. Nucleic acids research, 46(1), 25-41. https://doi.org/10.1093/nar/gkx1184