F. Le Page et al., Transcription-coupled repair of 8-oxoGuanine: Requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome, CELL, 101(2), 2000, pp. 159-171
Analysis of transcription-coupled repair (TCR) of oxidative lesions here re
veals strand-specific removal of 8-oxo-guanine (8-oxoG) and thymine glycol
both in normal human cells and xeroderma pigmentosum (XP) cells defective i
n nucleotide excision repair. In contrast, Cockayne syndrome (CS) cells inc
luding CS-B, XP-B/CS, XP-D/CS, and XP-G/CS not only lack TCR but cannot rem
ove 8-oxoG in a transcribed sequence, despite its proficient repair when no
t transcribed. The XP-G/CS defect uniquely slows lesion removal in nontrans
cribed sequences. Defective TCR leads to a mutation frequency at 8-oxoG of
30%-40% compared to the normal 1%-4%. Surprisingly, unrepaired 8-oxoG block
s transcription by RNA polymerase II. These data imply that TCR is required
for polymerase release to allow repair and that CS results from defects in
TCR of oxidative lesions.