Transcription-coupled repair of 8-oxoguanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome.

Abstract	Analysis of transcription-coupled repair (TCR) of oxidative lesions here reveals strand-specific removal of 8-oxo-guanine (8-oxoG) and thymine glycol both in normal human cells and xeroderma pigmentosum (XP) cells defective in nucleotide excision repair. In contrast, Cockayne syndrome (CS) cells including CS-B, XP-B/CS, XP-D/CS, and XP-G/CS not only lack TCR but cannot remove 8-oxoG in a transcribed sequence, despite its proficient repair when not transcribed. The XP-G/CS defect uniquely slows lesion removal in nontranscribed sequences. Defective TCR leads to a mutation frequency at 8-oxoG of 30%-40% compared to the normal 1%-4%. Surprisingly, unrepaired 8-oxoG blocks 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.
Authors	F Le Page, E E Kwoh, A Avrutskaya, A Gentil, S A Leadon, A Sarasin, P K Cooper
Journal	Cell (Cell) Vol. 101 Issue 2 Pg. 159-71 (Apr 14 2000) ISSN: 0092-8674 [Print] United States
PMID	10786832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S., Retracted Publication)
Chemical References	DNA excision repair protein ERCC-5 DNA-Binding Proteins Nuclear Proteins Poly-ADP-Ribose Binding Proteins Transcription Factors Transcription Factors, TFII Transcription Factor TFIIH 8-hydroxyguanine Guanine RNA Polymerase II Endonucleases DNA Helicases ERCC6 protein, human DNA Repair Enzymes
Topics	Cell Line Cockayne Syndrome (enzymology, genetics) DNA Helicases (genetics) DNA Repair (physiology) DNA Repair Enzymes DNA-Binding Proteins (genetics) Endonucleases Fibroblasts (cytology) Guanine (analogs & derivatives, metabolism) Humans Mutagenesis Nuclear Proteins Oxidation-Reduction Oxidative Stress (genetics) Plasmids Poly-ADP-Ribose Binding Proteins RNA Polymerase II (metabolism) Transcription Factor TFIIH Transcription Factors (genetics) Transcription Factors, TFII Transcription, Genetic (physiology) Transfection Xeroderma Pigmentosum (enzymology, genetics)

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