Cockayne syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo

Irina V Kovtun, Kurt O. Johnson, Cynthia T. McMurray

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)509-514
Number of pages6
JournalAging
Volume3
Issue number5
StatePublished - May 2011

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Cockayne Syndrome
Huntington Disease
DNA Repair
DNA
Proteins
IgA receptor

Keywords

  • Base excision DNA repair
  • CAG expansion
  • CSB
  • Huntington's disease
  • Transcription coupled repair

ASJC Scopus subject areas

  • Aging
  • Cell Biology
  • Geriatrics and Gerontology

Cite this

Cockayne syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo. / Kovtun, Irina V; Johnson, Kurt O.; McMurray, Cynthia T.

In: Aging, Vol. 3, No. 5, 05.2011, p. 509-514.

Research output: Contribution to journalArticle

Kovtun, IV, Johnson, KO & McMurray, CT 2011, 'Cockayne syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo', Aging, vol. 3, no. 5, pp. 509-514.
Kovtun, Irina V ; Johnson, Kurt O. ; McMurray, Cynthia T. / Cockayne syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo. In: Aging. 2011 ; Vol. 3, No. 5. pp. 509-514.
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