Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects

Fousteri, Maria; Mullenders, Leon H.F.

doi:10.1038/cr.2008.6

Cited by 404 publications

(352 citation statements)

References 95 publications

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“…Such mutations can be explained by replication of deaminated cytosine (uracil, which is read as thymine) and adenine (hypoxanthine, which is read as guanine resulting in A>G/T>C transition). However, in addition, the T>C mutations exhibit transcriptional strand bias, potentially indicating that some of these mutations arise from adducts subject to transcription coupled repair 9 . The signature 5 mutation rate is high in kidney clear cell and papillary cancers, which are thought to originate from kidney proximal tubular epithelium which absorbs metabolites, but low in kidney chromophobe tumours, which may arise from cells of the cortical collecting duct 10 .…”

Section: Resultsmentioning

confidence: 99%

Clock-like mutational processes in human somatic cells

et al. 2015

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During the course of a lifetime somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This study provides the first survey of clock-like mutational processes operative in human somatic cells.

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Section: Resultsmentioning

confidence: 99%

Clock-like mutational processes in human somatic cells

et al. 2015

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“…In GGR, 2 heterodimers XPC-RAD23B and UV-DDB (heterodimer of DDB1-DDB2) recognize DNA distortion and bind to the damaged site. 17,18 In TCR, RNA polymerase II gets blocked at the damaged site. This blockade is recognized and removed by the proteins ERCC6 (CSB) and ERCC8.…”

Section: Uiccmentioning

confidence: 99%

“…The resulting gap is filled by DNA polymerases d and e, and ligase I. 17,18 Although development of laryngeal cancer can widely be attributed to exogenous exposures by smoking and alcohol consumption, only a small portion of exposed individuals develop cancer, suggesting the involvement of genetic predisposition. 21,22 Genetic variations, e.g., single-nucleotide polymorphisms (SNPs), in important NER genes were hypothesized to modulate an individual's ability to repair tobacco smoke-induced DNA damage thus contributing to cancer susceptibility.…”

Section: Uiccmentioning

confidence: 99%

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Laryngeal cancer risk associated with smoking and alcohol consumption is modified by genetic polymorphisms in ERCC5, ERCC6 and RAD23B but not by polymorphisms in five other nucleotide excision repair genes

Abbasi

Ramroth

Becher

et al. 2009

Intl Journal of Cancer

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Laryngeal cancer is known to be associated with smoking and high alcohol consumption. Nucleotide excision repair (NER) plays a key role in repairing DNA damage induced by these exposures and might affect laryngeal cancer susceptibility. In a populationbased case-control study including 248 cases and 647 controls, the association of laryngeal cancer with 14 single nucleotide polymorphisms (SNPs) in 8 NER genes (XPC, XPA, ERCC1, ERCC2, ERCC4, ERCC5, ERCC6 and RAD23B) was analyzed with respect to smoking and alcohol exposure. For genotyping, sequence specific hybridization probes were used. Data were evaluated by conditional logistic regression analysis, stratified for age and gender, and adjusted for smoking, alcohol consumption and education. Pro-carriers of ERCC6 Arg1230Pro showed a decreased risk for laryngeal cancer (OR 5 0.53, 95% CI 0.34-0.85), strongest in heavy smokers and high alcohol consumers. ERCC5 Asp1104His was associated with risk in heavy smokers (OR 5 1.70, 95% CI 1.1-2.5). Val-carriers of RAD23B Ala249Val had an increased cancer risk in heavy smokers (OR 5 1.6, 95% CI 1.1-2.5) and high alcohol consumers (OR 5 2.0, 95% CI 1.1-3.4). The combined effect of smoking and alcohol intake affected risk, at high exposure level, for ERCC6 1230Pro carriers (OR 5 0.47, 95% CI 0.22-0.98) and RAD23B 249Val carriers (OR 5 2.6, 95% CI 1.3-4.9). When tested for gene-gene interaction, presence of 3 risk alleles in the XPC-RAD23B complex increased the risk 2.1-fold. SNPs in the other genes did not show a significant association with laryngeal cancer risk. We conclude that common genetic variations in NER genes can significantly modify laryngeal cancer risk. ' UICCKey words: genetic variation; population-based case-control study; haplotype; cancer susceptibility; gene-environment interaction Laryngeal cancer is the most frequent form of head and neck cancers in Germany and the second most common form of respiratory tract cancers in the US. 1,2 The average age of onset of the disease is 64 years and it is more common in males than in females (6:1 ratio).Cigarette smoking and alcohol consumption are well acknowledged risk factors for laryngeal cancer. [3][4][5][6][7] Cancer risk is directly related with duration and number of cigarettes smoked, and considerably increased in individuals consuming more than 50 g of alcohol per day. Tobacco smoke contains many carcinogens including a group of N-nitrosamines that produce carcinogenic methyl and pyridyloxobutyl DNA adducts. 8 A further constituent of tobacco smoke is the highly toxic acetaldehyde 9,10 which produces genotoxic 1,N 2 -propano-2 0 -deoxyguanosine DNA adducts. 9,11 Acetaldehyde is also an intermediate product of ethanol metabolism and its concentration increases in a multiplicative manner in individuals who are simultaneously smoking and drinking alcohol. 12 This observation might explain the synergistic and multiplicative effect found for alcohol and smoking in laryngeal cancer risk. 3,7 DNA repair is of fundamental importance in maintaining genomic stabilit...

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“…TCR is initiated when elongating RNA polymerase II (RNAPII) progression is blocked by damage in the transcribed strand. RNAPII complex must be displaced and/or degraded in order for efficient repair because it shields the DNA lesion and prevents accessibility of NER proteins (reviewed in Licht et al, 2003;Fousteri et al, 2008). Several models have been proposed regarding how CSB rescues RNAPII complexes that are stalled at DNA lesions (Selby et al, 1997;Tornaletti et al, 1999), but the details of this process remains unclear.…”

Section: The Role Of Csb In Various Cellular Processesmentioning

confidence: 99%

The role of Cockayne Syndrome group B (CSB) protein in base excision repair and aging

Stevnsner

Müftüoğlu

Aamann

et al. 2008

Mechanisms of Ageing and Development

123

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Cockayne Syndrome (CS) is a rare human genetic disorder characterized by progressive multisystem degeneration and segmental premature aging. The CS complementation group B (CSB) protein is engaged in transcription coupled and global nucleotide excision repair, base excision repair and general transcription. However, the precise molecular function of the CSB protein is still unclear. In the current review we discuss the involvement of CSB in some of these processes, with focus on the role of CSB in repair of oxidative damage, as deficiencies in the repair of these lesions may be an important aspect of the premature aging phenotype of CS.

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Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects

Cited by 404 publications

References 95 publications

Clock-like mutational processes in human somatic cells

Clock-like mutational processes in human somatic cells

Laryngeal cancer risk associated with smoking and alcohol consumption is modified by genetic polymorphisms in ERCC5, ERCC6 and RAD23B but not by polymorphisms in five other nucleotide excision repair genes

The role of Cockayne Syndrome group B (CSB) protein in base excision repair and aging

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