Isabel Mellon, University of Kentucky, Lexington, KY, USA
Published online: January 2006
DOI: 10.1038/npg.els.0005971
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.
|
| References | |
| Cooper PK, Nouspikel T, Clarkson SG and Leadon SA (1997) Defective transcription-coupled repair of oxidative base damage in Cockayne syndrome patients form XP group G. Science 275: 990–993. | |
| Le Page F, Klungland A, Barnes DE, Sarasin A and Boiteux S (2000) Transcription coupled repair of 8-oxoguanine in murine cells: The Ogg1 protein is required for repair in nontranscribed sequences but not in transcribed sequences. Proceedings of the National Academy of Sciences of the United States of America 97: 8397–8402. | |
| Mellon I, Spivak G and Hanawalt PC (1987) Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene. Cell 51: 241–249. | |
| Moolenaar GF, Monaco V, van der Marel GA, et al. (2000) The effect of the DNA flanking the lesion on formation of the UvrB–DNA preincision complex. Journal of Biological Chemistry 275: 8038–8043. | |
| Park J-S, Marr MT and Roberts JW (2002) E. coli transcription repair coupling factor (Mfd protein) rescues arrested complexes by promoting forward translocation. Cell 109: 757–767. | |
| Plosky B, Samson L, Engelward B, et al. (2002) Base excision repair and nucleotide excision repair contribute to the removal of N-methylpurines from active genes. DNA Repair 1: 683–696. | |
| Selby CP and Sancar A (1993) Molecular mechanism of transcription-repair coupling. Science 260: 53–58. | |
| Tornaletti S, Maeda LS, Lloyd DR, Reines D and Hanawalt PC (2001) Effect of thymine glycol on transcription elongation by T7 RNA polymerase and mammalian RNA polymerase II. Journal of Biological Chemistry 276: 45376–45371. | |
| Viswanathan A and Doetsch PW (1998) Effects of nonbulky DNA base damages on Escherichia coli RNA polymerase-mediated elongation and promoter clearance. Journal of Biological Chemistry 272: 21276–21281. | |
| Zou Y, Luo C and Geacintov NE (2001) Hierarchy of DNA damage recognition in Escherichia coli nucleotide excision repair. Biochemistry 40: 2923–2931. | |
| 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. | |
| book Friedberg EC, Walker GC and Siede W (1995) DNA Repair and Mutagenesis Washington, DC: ASM Press. | |
| Kamiuchi S, Saijo M, Citterio E, et al. (2002) Translocation of Cockayne syndrome group A protein to the nuclear matrix: possible relevance to transcription-coupled repair. Proceedings of the National Academy of Sciences of the United States of America 99: 201–206. | |
| 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. | |
| Sugasawa K, Ng JMY, Masutani CSI, et al. (1998) Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Molecular Cell 2: 223–232. | |
| Svejstrup JQ (2002) Mechanisms of transcription coupled DNA repair. Nature Reviews 3: 21–29. | |
| 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. | |
Copyright © 2000-2013 by John Wiley & Sons, Inc., or related companies. All rights reserved.
