TY - JOUR

T1 - Activity of Human Apurinic/Apyrimidinic Endonuclease APE1 Toward Damaged DNA and Native RNA With Non-canonical Structures

AU - Davletgildeeva, Anastasia T.

AU - Kuznetsova, Alexandra A.

AU - Fedorova, Olga S.

AU - Kuznetsov, Nikita A.

N1 - Funding Information: Funding. The experimental part of the work was supported by the Russian Science Foundation grant 18-14-00135. Partial salary support was received from the Russian Ministry of Higher Education and Science project # AAAA-A17-117020210022-4. Publisher Copyright: © Copyright © 2020 Davletgildeeva, Kuznetsova, Fedorova and Kuznetsov. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/10/30

Y1 - 2020/10/30

N2 - 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.

AB - 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.

KW - AP endonuclease

KW - DNA repair

KW - non-B-DNA

KW - nucleotide recognition

KW - quadruplex

KW - SITE

KW - CRYSTAL-STRUCTURE

KW - BASE EXCISION

KW - CONFORMATIONAL DYNAMICS

KW - ABASIC ENDONUCLEASE

KW - INCISION REPAIR PATHWAY

KW - DIVALENT METAL-IONS

KW - N-TERMINAL DOMAIN

KW - BINDING

KW - G-QUADRUPLEX

UR - http://www.scopus.com/inward/record.url?scp=85095991348&partnerID=8YFLogxK

U2 - 10.3389/fcell.2020.590848

DO - 10.3389/fcell.2020.590848

M3 - Article

C2 - 33195255

AN - SCOPUS:85095991348

VL - 8

JO - Frontiers in Cell and Developmental Biology

JF - Frontiers in Cell and Developmental Biology

SN - 2296-634X

M1 - 590848

ER -