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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...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2009
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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. |
format | Text |
id | pubmed-2705181 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
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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