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DNA Repair and DNA Triplet Repeat Expansion: The Impact of Abasic Lesions on Triplet Repeat DNA Energetics

[Image: see text] Enhanced levels of DNA triplet expansion are observed when base excision repair (BER) of oxidative DNA base damage (e.g., 8-oxo-dG) occurs at or near CAG repeat sequences. This observation suggests an interplay between processing mechanisms required for DNA repair and expansion pat...

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Autores principales: Völker, Jens, Plum, G. Eric, Klump, Horst H., Breslauer, Kenneth J.
Formato: Texto
Lenguaje:English
Publicado: American Chemical Society 2009
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705181/
https://www.ncbi.nlm.nih.gov/pubmed/19566100
http://dx.doi.org/10.1021/ja902161e
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author Völker, Jens
Plum, G. Eric
Klump, Horst H.
Breslauer, Kenneth J.
author_facet Völker, Jens
Plum, G. Eric
Klump, Horst H.
Breslauer, Kenneth J.
author_sort Völker, Jens
collection PubMed
description [Image: see text] Enhanced levels of DNA triplet expansion are observed when base excision repair (BER) of oxidative DNA base damage (e.g., 8-oxo-dG) occurs at or near CAG repeat sequences. This observation suggests an interplay between processing mechanisms required for DNA repair and expansion pathways that yield genotypes associated with many neurological/developmental disorders. It has been proposed that DNA expansion involves the transient formation within the triplet repeat domains of non-native slipped DNA structures that are incorrectly processed by the BER machinery of repair during DNA synthesis. We show here that replacement within a triplet repeat bulge loop domain of a guanosine residue by an abasic site, the universal BER intermediate, increases the population of slipped/looped DNA structures relative to the corresponding lesion-free construct. Such abasic lesion-induced energetic enhancement of slipped/looped structures provides a linkage between BER and DNA expansion. We discuss how the BER machinery of repair may be influenced by abasic-induced energetic alterations in the properties of regions proximal to and/or within triplet repeat domains, thereby potentially modulating levels of DNA expansion.
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spelling pubmed-27051812009-07-07 DNA Repair and DNA Triplet Repeat Expansion: The Impact of Abasic Lesions on Triplet Repeat DNA Energetics Völker, Jens Plum, G. Eric Klump, Horst H. Breslauer, Kenneth J. J Am Chem Soc [Image: see text] Enhanced levels of DNA triplet expansion are observed when base excision repair (BER) of oxidative DNA base damage (e.g., 8-oxo-dG) occurs at or near CAG repeat sequences. This observation suggests an interplay between processing mechanisms required for DNA repair and expansion pathways that yield genotypes associated with many neurological/developmental disorders. It has been proposed that DNA expansion involves the transient formation within the triplet repeat domains of non-native slipped DNA structures that are incorrectly processed by the BER machinery of repair during DNA synthesis. We show here that replacement within a triplet repeat bulge loop domain of a guanosine residue by an abasic site, the universal BER intermediate, increases the population of slipped/looped DNA structures relative to the corresponding lesion-free construct. Such abasic lesion-induced energetic enhancement of slipped/looped structures provides a linkage between BER and DNA expansion. We discuss how the BER machinery of repair may be influenced by abasic-induced energetic alterations in the properties of regions proximal to and/or within triplet repeat domains, thereby potentially modulating levels of DNA expansion. American Chemical Society 2009-06-15 2009-07-08 /pmc/articles/PMC2705181/ /pubmed/19566100 http://dx.doi.org/10.1021/ja902161e Text en Copyright © 2009 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. 40.75
spellingShingle Völker, Jens
Plum, G. Eric
Klump, Horst H.
Breslauer, Kenneth J.
DNA Repair and DNA Triplet Repeat Expansion: The Impact of Abasic Lesions on Triplet Repeat DNA Energetics
title DNA Repair and DNA Triplet Repeat Expansion: The Impact of Abasic Lesions on Triplet Repeat DNA Energetics
title_full DNA Repair and DNA Triplet Repeat Expansion: The Impact of Abasic Lesions on Triplet Repeat DNA Energetics
title_fullStr DNA Repair and DNA Triplet Repeat Expansion: The Impact of Abasic Lesions on Triplet Repeat DNA Energetics
title_full_unstemmed DNA Repair and DNA Triplet Repeat Expansion: The Impact of Abasic Lesions on Triplet Repeat DNA Energetics
title_short DNA Repair and DNA Triplet Repeat Expansion: The Impact of Abasic Lesions on Triplet Repeat DNA Energetics
title_sort dna repair and dna triplet repeat expansion: the impact of abasic lesions on triplet repeat dna energetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705181/
https://www.ncbi.nlm.nih.gov/pubmed/19566100
http://dx.doi.org/10.1021/ja902161e
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