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Human Ape2 protein has a 3′–5′ exonuclease activity that acts preferentially on mismatched base pairs

DNA damage, such as abasic sites and DNA strand breaks with 3′-phosphate and 3′-phosphoglycolate termini present cytotoxic and mutagenic threats to the cell. Class II AP endonucleases play a major role in the repair of abasic sites as well as of 3′-modified termini. Human cells contain two class II...

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Detalles Bibliográficos
Autores principales: Burkovics, Peter, Szukacsov, Valeria, Unk, Ildiko, Haracska, Lajos
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459411/
https://www.ncbi.nlm.nih.gov/pubmed/16687656
http://dx.doi.org/10.1093/nar/gkl259
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author Burkovics, Peter
Szukacsov, Valeria
Unk, Ildiko
Haracska, Lajos
author_facet Burkovics, Peter
Szukacsov, Valeria
Unk, Ildiko
Haracska, Lajos
author_sort Burkovics, Peter
collection PubMed
description DNA damage, such as abasic sites and DNA strand breaks with 3′-phosphate and 3′-phosphoglycolate termini present cytotoxic and mutagenic threats to the cell. Class II AP endonucleases play a major role in the repair of abasic sites as well as of 3′-modified termini. Human cells contain two class II AP endonucleases, the Ape1 and Ape2 proteins. Ape1 possesses a strong AP-endonuclease activity and weak 3′-phosphodiesterase and 3′–5′ exonuclease activities, and it is considered to be the major AP endonuclease in human cells. Much less is known about Ape2, but its importance is emphasized by the growth retardation and dyshematopoiesis accompanied by G2/M arrest phenotype of the APE2-null mice. Here, we describe the biochemical characteristics of human Ape2. We find that Ape2 exhibits strong 3′–5′ exonuclease and 3′-phosphodiesterase activities and has only a very weak AP-endonuclease activity. Mutation of the active-site residue Asp 277 to Ala in Ape2 inactivates all these activities. We also demonstrate that Ape2 preferentially acts at mismatched deoxyribonucleotides at the recessed 3′-termini of a partial DNA duplex. Based on these results we suggest a novel role for human Ape2 as a 3′–5′ exonuclease.
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spelling pubmed-14594112006-05-15 Human Ape2 protein has a 3′–5′ exonuclease activity that acts preferentially on mismatched base pairs Burkovics, Peter Szukacsov, Valeria Unk, Ildiko Haracska, Lajos Nucleic Acids Res Article DNA damage, such as abasic sites and DNA strand breaks with 3′-phosphate and 3′-phosphoglycolate termini present cytotoxic and mutagenic threats to the cell. Class II AP endonucleases play a major role in the repair of abasic sites as well as of 3′-modified termini. Human cells contain two class II AP endonucleases, the Ape1 and Ape2 proteins. Ape1 possesses a strong AP-endonuclease activity and weak 3′-phosphodiesterase and 3′–5′ exonuclease activities, and it is considered to be the major AP endonuclease in human cells. Much less is known about Ape2, but its importance is emphasized by the growth retardation and dyshematopoiesis accompanied by G2/M arrest phenotype of the APE2-null mice. Here, we describe the biochemical characteristics of human Ape2. We find that Ape2 exhibits strong 3′–5′ exonuclease and 3′-phosphodiesterase activities and has only a very weak AP-endonuclease activity. Mutation of the active-site residue Asp 277 to Ala in Ape2 inactivates all these activities. We also demonstrate that Ape2 preferentially acts at mismatched deoxyribonucleotides at the recessed 3′-termini of a partial DNA duplex. Based on these results we suggest a novel role for human Ape2 as a 3′–5′ exonuclease. Oxford University Press 2006 2006-05-10 /pmc/articles/PMC1459411/ /pubmed/16687656 http://dx.doi.org/10.1093/nar/gkl259 Text en © The Author 2006. Published by Oxford University Press. All rights reserved
spellingShingle Article
Burkovics, Peter
Szukacsov, Valeria
Unk, Ildiko
Haracska, Lajos
Human Ape2 protein has a 3′–5′ exonuclease activity that acts preferentially on mismatched base pairs
title Human Ape2 protein has a 3′–5′ exonuclease activity that acts preferentially on mismatched base pairs
title_full Human Ape2 protein has a 3′–5′ exonuclease activity that acts preferentially on mismatched base pairs
title_fullStr Human Ape2 protein has a 3′–5′ exonuclease activity that acts preferentially on mismatched base pairs
title_full_unstemmed Human Ape2 protein has a 3′–5′ exonuclease activity that acts preferentially on mismatched base pairs
title_short Human Ape2 protein has a 3′–5′ exonuclease activity that acts preferentially on mismatched base pairs
title_sort human ape2 protein has a 3′–5′ exonuclease activity that acts preferentially on mismatched base pairs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459411/
https://www.ncbi.nlm.nih.gov/pubmed/16687656
http://dx.doi.org/10.1093/nar/gkl259
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