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

Anastasia T. Davletgildeeva, Alexandra A. Kuznetsova, Olga S. Fedorova, Nikita A. Kuznetsov

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number590848
Number of pages14
JournalFrontiers in Cell and Developmental Biology
Volume8
DOIs
Publication statusPublished - 30 Oct 2020

Keywords

  • AP endonuclease
  • DNA repair
  • non-B-DNA
  • nucleotide recognition
  • quadruplex
  • SITE
  • CRYSTAL-STRUCTURE
  • BASE EXCISION
  • CONFORMATIONAL DYNAMICS
  • ABASIC ENDONUCLEASE
  • INCISION REPAIR PATHWAY
  • DIVALENT METAL-IONS
  • N-TERMINAL DOMAIN
  • BINDING
  • G-QUADRUPLEX

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