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

Journal International Journal of Molecular Sciences
, E-ISSN: 1422-0067
Output data Year: 2022, Volume: 23, Number: 5, Article number : 2869, Pages count : DOI: 10.3390/ijms23052869
Tags DNA repair; abasic site; damaged nucleotide; endonuclease activity; 3 '-5 ' exonuclease activity; apurinic/apyrimidinic endonuclease
Authors Davletgildeeva Anastasiia T. 1 , Kuznetsova Alexandra A. 1 , Novopashina Darya S. 1 , Ishchenko Alexander A. 2 , Saparbaev Murat 2 , Fedorova Olga S. 1 , Kuznetsov Nikita A. 1,3
Affiliations
1 (Данные Web of science) RAS, Inst Chem Biol & Fundamental Med, SB, Novosibirsk 630090, Russia
2 (Данные Web of science) Univ Paris Saclay, Grp Mech DNA Repair & Carcinogenesis, Gustave Roussy Canc Campus, CNRS UMR9019, F-94805 Villejuif, France
3 (Данные Web of science) Novosibirsk State Univ, Dept Nat Sci, Novosibirsk 630090, Russia

Abstract: Apurinic/apyrimidinic (AP)-endonucleases are multifunctional enzymes that are required for cell viability. AP-endonucleases incise DNA 5 & PRIME; to an AP-site; can recognize and process some damaged nucleosides; and possess 3 & PRIME;-phosphodiesterase, 3 & PRIME;-phosphatase, and endoribonuclease 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 humans (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 & PRIME;-5 & PRIME; exonuclease activity was the highest in hAPE1 among these enzymes. In contrast, the endoribonuclease activity of the enzymes could be ranked as hAPE1 & AP; zAPE1 & LE; xAPE1 & LE; 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.
Cite: Davletgildeeva A.T. , Kuznetsova A.A. , Novopashina D.S. , Ishchenko A.A. , Saparbaev M. , Fedorova O.S. , Kuznetsov N.A.
Comparative Analysis of Exo- and Endonuclease Activities of APE1-like Enzymes
International Journal of Molecular Sciences. 2022. V.23. N5. 2869 . DOI: 10.3390/ijms23052869 WOS Scopus OpenAlex
Dates:
Submitted: Mar 3, 2022
Accepted: Mar 4, 2022
Published print: Mar 6, 2022
Identifiers:
Web of science: WOS:000772933900001
Scopus: 2-s2.0-85125576961
OpenAlex: W4220665872
Citing:
DB Citing
Web of science 4
Scopus 3
OpenAlex 4
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