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Fidelity of DNA replication—a matter of proofreading

DNA that is transmitted to daughter cells must be accurately duplicated to maintain genetic integrity and to promote genetic continuity. A major function of replicative DNA polymerases is to replicate DNA with the very high accuracy. The fidelity of DNA replication relies on nucleotide selectivity o...

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Autores principales: Bębenek, Anna, Ziuzia-Graczyk, Izabela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153641/
https://www.ncbi.nlm.nih.gov/pubmed/29500597
http://dx.doi.org/10.1007/s00294-018-0820-1
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author Bębenek, Anna
Ziuzia-Graczyk, Izabela
author_facet Bębenek, Anna
Ziuzia-Graczyk, Izabela
author_sort Bębenek, Anna
collection PubMed
description DNA that is transmitted to daughter cells must be accurately duplicated to maintain genetic integrity and to promote genetic continuity. A major function of replicative DNA polymerases is to replicate DNA with the very high accuracy. The fidelity of DNA replication relies on nucleotide selectivity of replicative DNA polymerase, exonucleolytic proofreading, and postreplicative DNA mismatch repair (MMR). Proofreading activity that assists most of the replicative polymerases is responsible for removal of incorrectly incorporated nucleotides from the primer terminus before further primer extension. It is estimated that proofreading improves the fidelity by a 2–3 orders of magnitude. The primer with the incorrect terminal nucleotide has to be moved to exonuclease active site, and after removal of the wrong nucleotide must be transferred back to polymerase active site. The mechanism that allows the transfer of the primer between pol and exo site is not well understood. While defects in MMR are well known to be linked with increased cancer incidence only recently, the replicative polymerases that have alterations in the exonuclease domain have been associated with some sporadic and hereditary human cancers. In this review, we would like to emphasize the importance of proofreading (3′-5′ exonuclease activity) in the fidelity of DNA replication and to highlight what is known about switching from polymerase to exonuclease active site.
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spelling pubmed-61536412018-10-04 Fidelity of DNA replication—a matter of proofreading Bębenek, Anna Ziuzia-Graczyk, Izabela Curr Genet Review DNA that is transmitted to daughter cells must be accurately duplicated to maintain genetic integrity and to promote genetic continuity. A major function of replicative DNA polymerases is to replicate DNA with the very high accuracy. The fidelity of DNA replication relies on nucleotide selectivity of replicative DNA polymerase, exonucleolytic proofreading, and postreplicative DNA mismatch repair (MMR). Proofreading activity that assists most of the replicative polymerases is responsible for removal of incorrectly incorporated nucleotides from the primer terminus before further primer extension. It is estimated that proofreading improves the fidelity by a 2–3 orders of magnitude. The primer with the incorrect terminal nucleotide has to be moved to exonuclease active site, and after removal of the wrong nucleotide must be transferred back to polymerase active site. The mechanism that allows the transfer of the primer between pol and exo site is not well understood. While defects in MMR are well known to be linked with increased cancer incidence only recently, the replicative polymerases that have alterations in the exonuclease domain have been associated with some sporadic and hereditary human cancers. In this review, we would like to emphasize the importance of proofreading (3′-5′ exonuclease activity) in the fidelity of DNA replication and to highlight what is known about switching from polymerase to exonuclease active site. Springer Berlin Heidelberg 2018-03-02 2018 /pmc/articles/PMC6153641/ /pubmed/29500597 http://dx.doi.org/10.1007/s00294-018-0820-1 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review
Bębenek, Anna
Ziuzia-Graczyk, Izabela
Fidelity of DNA replication—a matter of proofreading
title Fidelity of DNA replication—a matter of proofreading
title_full Fidelity of DNA replication—a matter of proofreading
title_fullStr Fidelity of DNA replication—a matter of proofreading
title_full_unstemmed Fidelity of DNA replication—a matter of proofreading
title_short Fidelity of DNA replication—a matter of proofreading
title_sort fidelity of dna replication—a matter of proofreading
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153641/
https://www.ncbi.nlm.nih.gov/pubmed/29500597
http://dx.doi.org/10.1007/s00294-018-0820-1
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