TY - JOUR
T1 - Cockayne syndrome B protein antagonizes OGG1 in modulating CAG repeat length in vivo
AU - Kovtun, Irina V.
AU - Johnson, Kurt O.
AU - McMurray, Cynthia T.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
KW - Base excision DNA repair
KW - CAG expansion
KW - CSB
KW - Huntington's disease
KW - Transcription coupled repair
UR - http://www.scopus.com/inward/record.url?scp=79960328293&partnerID=8YFLogxK
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U2 - 10.18632/aging.100324
DO - 10.18632/aging.100324
M3 - Article
C2 - 21566259
AN - SCOPUS:79960328293
SN - 1945-4589
VL - 3
SP - 509
EP - 514
JO - Aging
JF - Aging
IS - 5
ER -