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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
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Retracted Publication
MeSH terms
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Cell Line
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Cockayne Syndrome / enzymology
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Cockayne Syndrome / genetics*
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DNA Helicases / genetics*
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DNA Repair / physiology
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DNA Repair Enzymes
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DNA-Binding Proteins / genetics*
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Endonucleases
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Fibroblasts / cytology
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Guanine / analogs & derivatives*
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Guanine / metabolism
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Humans
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Mutagenesis
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Nuclear Proteins
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Oxidation-Reduction
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Oxidative Stress / genetics
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Plasmids
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Poly-ADP-Ribose Binding Proteins
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RNA Polymerase II / metabolism
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Transcription Factor TFIIH
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Transcription Factors / genetics*
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Transcription Factors, TFII*
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Transcription, Genetic / physiology
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Transfection
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Xeroderma Pigmentosum / enzymology
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Xeroderma Pigmentosum / genetics*
Substances
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DNA excision repair protein ERCC-5
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DNA-Binding Proteins
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Nuclear Proteins
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Poly-ADP-Ribose Binding Proteins
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Transcription Factors
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Transcription Factors, TFII
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Transcription Factor TFIIH
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8-hydroxyguanine
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Guanine
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RNA Polymerase II
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Endonucleases
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DNA Helicases
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ERCC6 protein, human
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DNA Repair Enzymes