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Molecules 2011, 16(9), 7994-8019; doi:10.3390/molecules16097994

Exploiting the Nucleotide Substrate Specificity of Repair DNA Polymerases To Develop Novel Anticancer Agents

DNA Enzymology & Molecular Virology, Insititute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy
Author to whom correspondence should be addressed.
Received: 5 July 2011 / Revised: 26 August 2011 / Accepted: 13 September 2011 / Published: 16 September 2011
(This article belongs to the Special Issue Nucleoside Analogues)
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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.
Keywords: DNA repair; cancer; DNA polymerase; nucleoside analogs DNA repair; cancer; DNA polymerase; nucleoside analogs

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Crespan, E.; Garbelli, A.; Amoroso, A.; Maga, G. Exploiting the Nucleotide Substrate Specificity of Repair DNA Polymerases To Develop Novel Anticancer Agents. Molecules 2011, 16, 7994-8019.

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