Effect of the Substrate Structure and Metal Ions on the Hydrolysis of Undamaged RNA by Human AP Endonuclease APE1

Overview

Journal Acta Naturae

Specialty Biology

Date 2020 Aug 4

PMID 32742730

Citations 9

Authors

A A Kuznetsova

D S Novopashina

O S Fedorova

N A Kuznetsov

Affiliations

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Abstract

Human apurinic/apyrimidinic (AP) endonuclease APE1 is one of the participants in the DNA base excision repair. The main biological function of APE1 is to hydrolyze the phosphodiester bond on the 5'-side of the AP sites. It has been shown recently that APE1 acts as an endoribonuclease and can cleave mRNA, thereby controlling the level of some transcripts. The sequences of CA, UA, and UG dinucleotides are the cleavage sites in RNA. In the present work, we performed a comparative analysis of the cleavage efficiency of model RNA substrates with short hairpin structures in which the loop size and the location of the pyrimidine-purine dinucleotide sequence were varied. The effect of various divalent metal ions and pH on the efficiency of the endoribonuclease reaction was analyzed. It was shown that site-specific hydrolysis of model RNA substrates depends on the spatial structure of the substrate. In addition, RNA cleavage occured in the absence of divalent metal ions, which proves that hydrolysis of DNA- and RNA substrates occurs via different catalytic mechanisms.

Citing Articles

Kinetic Features of Degradation of R-Loops by RNase H1 from .

Kuznetsova A, Kosarev I, Timofeyeva N, Novopashina D, Kuznetsov N Int J Mol Sci. 2024; 25(22).

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Inner Amino Acid Contacts Are Key Factors of Multistage Structural Rearrangements of DNA and Affect Substrate Specificity of Apurinic/Apyrimidinic Endonuclease APE1.

Bulygin A, Syryamina V, Kuznetsova A, Novopashina D, Dzuba S, Kuznetsov N Int J Mol Sci. 2023; 24(14).

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Kinetic Features of 3'-5'-Exonuclease Activity of Apurinic/Apyrimidinic Endonuclease Apn2 from .

Kuznetsova A, Gavrilova A, Ishchenko A, Saparbaev M, Fedorova O, Kuznetsov N Int J Mol Sci. 2022; 23(22).

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

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The base excision repair process: comparison between higher and lower eukaryotes.

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