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Exploiting the Nucleotide Substrate Specificity of Repair DNA Polymerases To Develop Novel Anticancer Agents
The genome is constantly exposed to mutations that can originate during replication or as a result of the action of both endogenous and/or exogenous damaging agents [such as reactive oxygen species (ROS), UV light, genotoxic environmental compounds, etc.]. Cells have developed a set of specialized m...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264456/ https://www.ncbi.nlm.nih.gov/pubmed/21926946 http://dx.doi.org/10.3390/molecules16097994 |
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author | Crespan, Emmanuele Garbelli, Anna Amoroso, Alessandra Maga, Giovanni |
author_facet | Crespan, Emmanuele Garbelli, Anna Amoroso, Alessandra Maga, Giovanni |
author_sort | Crespan, Emmanuele |
collection | PubMed |
description | The genome is constantly exposed to mutations that can originate during replication or as a result of the action of both endogenous and/or exogenous damaging agents [such as reactive oxygen species (ROS), UV light, genotoxic environmental compounds, etc.]. Cells have developed a set of specialized mechanisms to counteract this mutational burden. Many cancer cells have defects in one or more DNA repair pathways, hence they rely on a narrower set of specialized DNA repair mechanisms than normal cells. Inhibiting one of these pathways in the context of an already DNA repair-deficient genetic background, will be more toxic to cancer cells than to normal cells, a concept recently exploited in cancer chemotherapy by the synthetic lethality approach. Essential to all DNA repair pathways are the DNA pols. Thus, these enzymes are being regarded as attractive targets for the development of specific inhibitors of DNA repair in cancer cells. In this review we examine the current state-of-the-art in the development of nucleotide analogs as inhibitors of repair DNA polymerases. |
format | Online Article Text |
id | pubmed-6264456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62644562018-12-10 Exploiting the Nucleotide Substrate Specificity of Repair DNA Polymerases To Develop Novel Anticancer Agents Crespan, Emmanuele Garbelli, Anna Amoroso, Alessandra Maga, Giovanni Molecules Review The genome is constantly exposed to mutations that can originate during replication or as a result of the action of both endogenous and/or exogenous damaging agents [such as reactive oxygen species (ROS), UV light, genotoxic environmental compounds, etc.]. Cells have developed a set of specialized mechanisms to counteract this mutational burden. Many cancer cells have defects in one or more DNA repair pathways, hence they rely on a narrower set of specialized DNA repair mechanisms than normal cells. Inhibiting one of these pathways in the context of an already DNA repair-deficient genetic background, will be more toxic to cancer cells than to normal cells, a concept recently exploited in cancer chemotherapy by the synthetic lethality approach. Essential to all DNA repair pathways are the DNA pols. Thus, these enzymes are being regarded as attractive targets for the development of specific inhibitors of DNA repair in cancer cells. In this review we examine the current state-of-the-art in the development of nucleotide analogs as inhibitors of repair DNA polymerases. MDPI 2011-09-16 /pmc/articles/PMC6264456/ /pubmed/21926946 http://dx.doi.org/10.3390/molecules16097994 Text en © 2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Review Crespan, Emmanuele Garbelli, Anna Amoroso, Alessandra Maga, Giovanni Exploiting the Nucleotide Substrate Specificity of Repair DNA Polymerases To Develop Novel Anticancer Agents |
title | Exploiting the Nucleotide Substrate Specificity of Repair DNA Polymerases To Develop Novel Anticancer Agents |
title_full | Exploiting the Nucleotide Substrate Specificity of Repair DNA Polymerases To Develop Novel Anticancer Agents |
title_fullStr | Exploiting the Nucleotide Substrate Specificity of Repair DNA Polymerases To Develop Novel Anticancer Agents |
title_full_unstemmed | Exploiting the Nucleotide Substrate Specificity of Repair DNA Polymerases To Develop Novel Anticancer Agents |
title_short | Exploiting the Nucleotide Substrate Specificity of Repair DNA Polymerases To Develop Novel Anticancer Agents |
title_sort | exploiting the nucleotide substrate specificity of repair dna polymerases to develop novel anticancer agents |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264456/ https://www.ncbi.nlm.nih.gov/pubmed/21926946 http://dx.doi.org/10.3390/molecules16097994 |
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