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

Aging (Albany NY). 2011 May;3(5):509-14. doi: 10.18632/aging.100324.


OGG1 and MSH2/MSH3 promote CAG repeat expansion at Huntington's disease (HD) locusin 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • DNA Glycosylases / genetics
  • DNA Glycosylases / metabolism
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Repair
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • Female
  • Humans
  • Huntington Disease / genetics
  • Huntington Disease / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Poly-ADP-Ribose Binding Proteins
  • Trinucleotide Repeat Expansion*


  • Poly-ADP-Ribose Binding Proteins
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes