Comparative Analysis of Exo-and Endonuclease Activities of APE1-like Enzymes

Anastasiia T. Davletgildeeva, Alexandra A. Kuznetsova, Darya S. Novopashina, Alexander A. Ishchenko, Murat Saparbaev, Olga S. Fedorova, Nikita A. Kuznetsov

Research output: Contribution to journalArticlepeer-review

Abstract

Apurinic/apyrimidinic (AP)-endonucleases are multifunctional enzymes that are required for cell viability. AP-endonucleases incise DNA 5′ to an AP-site; can recognize and process some damaged nucleosides; and possess 3′-phosphodiesterase, 3′-phosphatase, and endoribonu-clease activities. To elucidate the mechanism of substrate cleavage in detail, we analyzed the effect of mono-and divalent metal ions on the exo-and endonuclease activities of four homologous APE1-like endonucleases (from an insect (Rrp1), amphibian (xAPE1), fish (zAPE1), and from hu-mans (hAPE1)). It was found that the enzymes had similar patterns of dependence on metal ions’ concentrations in terms of AP-endonuclease activity, suggesting that the main biological function (AP-site cleavage) was highly conserved among evolutionarily distant species. The efficiency of the 3′-5′ exonuclease activity was the highest in hAPE1 among these enzymes. In contrast, the en-doribonuclease activity of the enzymes could be ranked as hAPE1 ≈ zAPE1 ≤ xAPE1 ≤ Rrp1. Taken together, the results revealed that the tested enzymes differed significantly in their capacity for substrate cleavage, even though the most important catalytic and substrate-binding amino acid residues were conserved. It can be concluded that substrate specificity and cleavage efficiency were controlled by factors external to the catalytic site, e.g., the N-terminal domain of these enzymes.

Original languageEnglish
Article number2869
JournalInternational Journal of Molecular Sciences
Volume23
Issue number5
DOIs
Publication statusPublished - 1 Mar 2022

Keywords

  • 3′-5′ exonuclease activity
  • Abasic site
  • Apurinic/apyrimidinic endonuclease
  • Damaged nucleotide
  • DNA repair
  • Endonuclease activity

OECD FOS+WOS

  • 1.04 CHEMICAL SCIENCES
  • 2.04 CHEMICAL ENGINEERING
  • 1.06 BIOLOGICAL SCIENCES

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