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APE1: A skilled nucleic acid surgeon

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 multif...

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Detalles Bibliográficos
Autores principales: Whitaker, Amy M., Freudenthal, Bret D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491353/
https://www.ncbi.nlm.nih.gov/pubmed/30170830
http://dx.doi.org/10.1016/j.dnarep.2018.08.012
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author Whitaker, Amy M.
Freudenthal, Bret D.
author_facet Whitaker, Amy M.
Freudenthal, Bret D.
author_sort Whitaker, Amy M.
collection PubMed
description 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.
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spelling pubmed-64913532019-04-30 APE1: A skilled nucleic acid surgeon Whitaker, Amy M. Freudenthal, Bret D. DNA Repair (Amst) Article 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. Elsevier B.V. 2018-11 2018-08-23 /pmc/articles/PMC6491353/ /pubmed/30170830 http://dx.doi.org/10.1016/j.dnarep.2018.08.012 Text en © 2018 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Whitaker, Amy M.
Freudenthal, Bret D.
APE1: A skilled nucleic acid surgeon
title APE1: A skilled nucleic acid surgeon
title_full APE1: A skilled nucleic acid surgeon
title_fullStr APE1: A skilled nucleic acid surgeon
title_full_unstemmed APE1: A skilled nucleic acid surgeon
title_short APE1: A skilled nucleic acid surgeon
title_sort ape1: a skilled nucleic acid surgeon
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491353/
https://www.ncbi.nlm.nih.gov/pubmed/30170830
http://dx.doi.org/10.1016/j.dnarep.2018.08.012
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