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APE1: A skilled nucleic acid surgeon.

Authors
  • Whitaker, Amy M1
  • Freudenthal, Bret D2
  • 1 Department of Biochemistry and Molecular Biology, Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
  • 2 Department of Biochemistry and Molecular Biology, Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: [email protected]
Type
Published Article
Journal
DNA repair
Publication Date
Nov 01, 2018
Volume
71
Pages
93–100
Identifiers
DOI: 10.1016/j.dnarep.2018.08.012
PMID: 30170830
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Before a deleterious DNA lesion can be replaced with its undamaged counterpart, the lesion must first be removed from the genome. This process of removing and replacing DNA lesions is accomplished by the careful coordination of several protein factors during DNA repair. One such factor is the multifunctional enzyme human apurinic/apyrimidinic endonuclease 1 (APE1), known best for its DNA backbone cleavage activity at AP sites during base excision repair (BER). APE1 preforms AP site incision with surgical precision and skill, by sculpting the DNA to place the cleavage site in an optimal position for nucleophilic attack within its compact protein active site. APE1, however, has demonstrated broad surgical expertise, and applies its DNA cleavage activity to a wide variety of DNA and RNA substrates. Here, we discuss what is known and unknown about APE1 cleavage mechanisms, focusing on structural and mechanistic considerations. Importantly, disruptions in the biological functions associated with APE1 are linked to numerous human maladies, including cancer and neurodegenerative diseases. The continued elucidation of APE1 mechanisms is required for rational drug design towards novel and strategic ways to target its associated repair pathways. Copyright © 2018 Elsevier B.V. All rights reserved.

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