Transcription-coupled repair of 8-oxoGuanine: Requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome

Citation
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
Citations number
69
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL
ISSN journal
00928674 → ACNP
Volume
101
Issue
2
Year of publication
2000
Pages
159 - 171
Database
ISI
SICI code
0092-8674(20000414)101:2<159:TRO8RF>2.0.ZU;2-D
Abstract
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.