Role of Transcription-Coupled DNA Repair in Susceptibility to Environmental Carcinogenesis

Hanawalt, Philip C.

doi:10.2307/3432821

Cited by 8 publications

(10 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…( 3,5 ) This phenomenon has been considered to be one of the characteristics of mutations caused by DNA adducts derived from exogenous carcinogens, such as smoke mutagens. ( 5,35–38 )…”

Section: Discussionmentioning

confidence: 99%

Etiologic value of p53 mutation spectra and differences with histology in lung cancers

et al. 2008

View full text Add to dashboard Cite

A total of 297 resected Japanese non-small cell lung cancers (74 squamous cell carcinomas and 223 adenocarcinomas) were analyzed to evaluate the validity of the p53 mutation spectrum as a fingerprint for mutagenic substances as etiological factors. Frequencies of G→ → → →T transversions in smokers were significantly higher than in non-smokers (P = 0.003) and the average incidence of G→ → → →T at hot spot codons of adduct formation was higher than that in other codons in smokers and in the hot spots in non-smokers. Further, the mutation showed a marked strand bias. G→ → → →A transitions at CpG sites (CpG→ → → →CpA) were equally distributed in smokers and non-smokers, and on both strands. A→ → → →G transitions did not show any variation with smoking status in terms of frequency, but exhibited a marked strand bias. Taken together, the G→ → → →T may be a fingerprint of direct mutagenic action of tobaccorelated compounds, the A→ → → →G being a new marker for other environmental chemicals, while the CpG→ → → →CpA may be attributable to endogenous spontaneous mutation, for active in lung carcinogenesis. (Cancer Sci 2008; 99: 287-295)

show abstract

“…( 3,5 ) This phenomenon has been considered to be one of the characteristics of mutations caused by DNA adducts derived from exogenous carcinogens, such as smoke mutagens. ( 5,35–38 )…”

Section: Discussionmentioning

confidence: 99%

Etiologic value of p53 mutation spectra and differences with histology in lung cancers

et al. 2008

View full text Add to dashboard Cite

show abstract

“…According to current models [19,24,41] transcription forks stalled at a lesion in the transcribed strand form a structure that can initiate the so-called transcription-coupled subpathway of NER (TC-NER) without the need of damage recognition by the XPC/HR23B and/or DDB complexes, but still requiring all the other NER factors. We find here that illudin lesions do interfere with transcription, and require TC-NER to recover.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumour compounds illudin S and Irofulven induce DNA lesions ignored by global repair and exclusively processed by transcription- and replication-coupled repair pathways

et al. 2002

View full text Add to dashboard Cite

Illudin S is a natural sesquiterpene drug with strong anti-tumour activity. Inside cells, unstable active metabolites of illudin cause the formation of as yet poorly characterised DNA lesions. In order to identify factors involved in their repair, we have performed a detailed genetic survey of repair-defective mutants for responses to the drug. We show that 90% of illudin's lethal effects in human fibroblasts can be prevented by an active nucleotide excision repair (NER) system. Core NER enzymes XPA, XPF, XPG, and TFIIH are essential for recovery. However, the presence of global NER initiators XPC, HR23A/HR23B and XPE is not required, whereas survival, repair and recovery from transcription inhibition critically depend on CSA, CSB and UVS, the factors specific for transcription-coupled NER. Base excision repair and non-homologous end-joining of DNA breaks do not play a major role in the processing of illudin lesions. However, active RAD18 is required for optimal cell survival, indicating that the lesions also block replication forks, eliciting post-replication-repair-like responses. However, the translesion-polymerase DNA pol eta is not involved. We conclude that illudin-induced lesions are exceptional in that they appear to be ignored by all of the known global repair systems, and can only be repaired when trapped in stalled replication or transcription complexes. We show that the semisynthetic illudin derivative hydroxymethylacylfulvene (HMAF, Irofulven), currently under clinical trial for anti-tumour therapy, acts via the same mechanism.

show abstract

“…These results thus suggested a general phenomenon that additional DNA glycosylases are present in mammalian cells, specific for repair of transcribed genes, which, unlike repair of the bulk of the genome, is critical for proper cellular functioning and survival (14). The dichotomy in repair of the bulk of the genome versus repair of transcribed sequences was recognized first in the nucleotide excision repair process and named global genome repair (GGR) and transcription-coupled repair (TCR), respectively (15).…”

mentioning

confidence: 99%

The discovery of a new family of mammalian enzymes for repair of oxidatively damaged DNA, and its physiological implications

Hazra¹

2003

Carcinogenesis

View full text Add to dashboard Cite

Oxidatively damaged bases in the genome are likely to be responsible for mutations leading to sporadic carcinogenesis. Two structurally similar DNA glycosylases, NTH1 and OGG1, which are able to excise most of these damaged bases, were identified previously in mammalian cells. A distinct family, consisting of two human DNA glycosylases orthologous to enzymes in Escherichia coli, has recently been characterized; they have overlapping substrate ranges with NTH1 and OGG1. The presence of multiple enzymes with potential back-up functions underscores the importance of removing both endogenously and exogenously generated oxidatively damaged bases from the genome, and may explain why no cancer or other disease phenotype has so far been linked to the deficiency of a single DNA glycosylase.

show abstract

Role of Transcription-Coupled DNA Repair in Susceptibility to Environmental Carcinogenesis

Abstract: 547-551 (1996)

Cited by 8 publications

References 17 publications

Etiologic value of p53 mutation spectra and differences with histology in lung cancers

Etiologic value of p53 mutation spectra and differences with histology in lung cancers

Anti-tumour compounds illudin S and Irofulven induce DNA lesions ignored by global repair and exclusively processed by transcription- and replication-coupled repair pathways

The discovery of a new family of mammalian enzymes for repair of oxidatively damaged DNA, and its physiological implications

Contact Info

Product

Resources

About