Transcription‐coupled DNA Repair

Abstract

Excision repair pathways remove a wide variety of lesions formed by endogenous and environmental agents, and protect humans from the mutagenic and carcinogenic consequences of persisting damage. Transcription‐coupled repair is a subpathway of excision repair that selectively removes lesions from the transcribed strands of expressed genes.

Keywords: nucleotide excision repair; base excision repair; transcription; ribonucleic acid polymerase; ultraviolet light

Figure 1.

Model for transcription‐coupled repair in E. coli. Elongating RNA polymerase complex (RNA pol; large oval) stalls at a cyclobutane pyrimidine dimer (CPD; small shaded square) in the transcribed strand. The polymerase complex, transcription bubble and nascent RNA translocate backwards. The mutation frequency decline protein Mfd (small oval) binds backtracked polymerase and DNA upstream of the bubble. Mfd promotes the forward translocation of the polymerase complex. The protein UvrB (triangle) binds 5′ (relative to the damaged strand), loads onto the forward edge of the bubble and translocates to the lesion. The polymerase complex backtracks or is dissociated by Mfd. Subsequent nucleotide excision repair (NER) processing events continue as they would in nontranscribed DNA. (After Park et al., .)

Figure 2.

Model for transcription‐coupled repair in mammalian cells. Elongating RNA polymerase complex (RNA pol; large oval) stalls at a cyclobutane pyrimidine dimer (CPD; small shaded square) in the transcribed strand. The polymerase complex, transcription bubble and nascent RNA translocate backwards. Proteins CSB and XAB2 (small ovals) bind the backtracked polymerase complex and promote forward translocation. General transcription factor TFIIH (triangle) binds 5′ to the damage and loads onto the forward edge of the bubble. The polymerase backtracks and is held at the nuclear matrix by CSA or dissociates. Subsequent NER events continue as they would in nontranscribed DNA.

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References

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Further Reading

Batty DP and Wood RD (2000) Damage recognition in nucleotide excision repair of DNA. Gene 241: 193–204.

Engstrom J, Larsen S, Rogers S and Bockrath R (1984) UV‐mutagenesis at a cloned target sequence: converted suppressor mutation is insensitive to mutation frequency decline regardless of the gene orientation. Mutation Research 132: 143–152.

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Mellon I and Hanawalt PC (1989) Induction of the Escherichia coli lactose operon selectively increases repair of its transcribed DNA strand. Nature 342: 95–98.

Scicchitano DA and Mellon I (1997) Transcription and DNA damage: a link to a kink. Environmental Health Perspectives 105: 145–153.

Spivak G, Itoh T, Matsunaga T, et al. (2002) Ultraviolet‐sensitive syndrome cells are defective in transcription‐coupled repair of cyclobutane pyrimidine dimers. DNA Repair 50: 1–15.

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Tornaletti S, Reines D and Hanawalt PC (1999) Structural characterization of RNA polymerase II complexes arrested by a cyclobutane pyrimidine dimer in the transcribed strand of template DNA. Journal of Biological Chemistry 274: 24124–24130.

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How to Cite close
Mellon, Isabel(Jan 2006) Transcription‐coupled DNA Repair. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005971]