Activity of Human Apurinic/Apyrimidinic Endonuclease APE1 Toward Damaged DNA and Native RNA With Non-canonical Structures

Frontiers in Cell and Developmental Biology
Anastasia T DavletgildeevaNikita A Kuznetsov

Abstract

The primary role of apurinic/apyrimidinic (AP) endonuclease APE1 in human cells is the cleavage of the sugar phosphate backbone 5' to an AP site in DNA to produce a single-strand break with a 5'-deoxyribose phosphate and 3'-hydroxyl end groups. APE1 can also recognize and incise some damaged or modified nucleotides and possesses some minor activities: 3'-5' exonuclease, 3'-phosphodiesterase, 3'-phosphatase, and RNase H. A molecular explanation for the discrimination of structurally different substrates by the single active site of the enzyme remains elusive. Here, we report a mechanism of target nucleotide recognition by APE1 as revealed by the results of an analysis of the APE1 process involving damaged DNA and native RNA substrates with non-canonical structures. The mechanism responsible for substrate specificity proved to be directly related to the ability of a target nucleotide to get into the active site of APE1 in response to an enzyme-induced DNA distortion.

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Methods Mentioned

BETA
FRET
electrophoresis
Fluorescence
Microscale Thermophoresis

Software Mentioned

Origin
MST
DynaFit
Gel
Pro Analyzer

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