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Cockayne Syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo
OGG1 and MSH2/MSH3 promote CAG repeat expansion at Huntington's disease (HD) locus in vivo during removal of oxidized bases from DNA. CSB, a transcription-coupled repair (TCR) protein, facilitates repair of some of the same oxidative lesions. In vitro, a knock down CSB results in a reduction of...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156601/ https://www.ncbi.nlm.nih.gov/pubmed/21566259 |
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author | Kovtun, Irina V. Johnson, Kurt O. McMurray, Cynthia T. |
author_facet | Kovtun, Irina V. Johnson, Kurt O. McMurray, Cynthia T. |
author_sort | Kovtun, Irina V. |
collection | PubMed |
description | OGG1 and MSH2/MSH3 promote CAG repeat expansion at Huntington's disease (HD) locus in vivo during removal of oxidized bases from DNA. CSB, a transcription-coupled repair (TCR) protein, facilitates repair of some of the same oxidative lesions. In vitro, a knock down CSB results in a reduction of transcription-induced deletions at CAG repeat tract. To test the role of CSB in vivo, we measured intergenerational and somatic expansion of CAG tracts in HD mice lacking CSB, OGG1, or both. We provide evidence that CSB protects CAG repeats from expansion by either active reduction of the tract length during parent-child transmission, or by antagonizing the action of OGG1, which tends to promote expansion in somatic cells. These results raise a possibility that actions of transcription-coupled and base excision repair pathways lead to different outcomes at CAG tracts in vivo. |
format | Online Article Text |
id | pubmed-3156601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-31566012011-08-17 Cockayne Syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo Kovtun, Irina V. Johnson, Kurt O. McMurray, Cynthia T. Aging (Albany NY) Research Paper OGG1 and MSH2/MSH3 promote CAG repeat expansion at Huntington's disease (HD) locus in vivo during removal of oxidized bases from DNA. CSB, a transcription-coupled repair (TCR) protein, facilitates repair of some of the same oxidative lesions. In vitro, a knock down CSB results in a reduction of transcription-induced deletions at CAG repeat tract. To test the role of CSB in vivo, we measured intergenerational and somatic expansion of CAG tracts in HD mice lacking CSB, OGG1, or both. We provide evidence that CSB protects CAG repeats from expansion by either active reduction of the tract length during parent-child transmission, or by antagonizing the action of OGG1, which tends to promote expansion in somatic cells. These results raise a possibility that actions of transcription-coupled and base excision repair pathways lead to different outcomes at CAG tracts in vivo. Impact Journals LLC 2011-05-03 /pmc/articles/PMC3156601/ /pubmed/21566259 Text en Copyright: © 2011 Kovtun et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Paper Kovtun, Irina V. Johnson, Kurt O. McMurray, Cynthia T. Cockayne Syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo |
title | Cockayne Syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo |
title_full | Cockayne Syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo |
title_fullStr | Cockayne Syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo |
title_full_unstemmed | Cockayne Syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo |
title_short | Cockayne Syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo |
title_sort | cockayne syndrome b protein antagonizes ogg1 in modulating cag repeat length in vivo |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156601/ https://www.ncbi.nlm.nih.gov/pubmed/21566259 |
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