Transcription-Coupled Repair of 8-oxoguanine: Requirement for XPG, TFIIH, and CSB and Implications for Cockayne Syndrome

Page, Florence Le; Kwoh, Ely; Avrutskaya, Anna V.; Gentil, A.; Leadon, Steven A.; Sarasin, Alain; Cooper, Priscilla K.

doi:10.1016/j.cell.2005.11.005

Cited by 143 publications

(83 citation statements)

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“…Faulty repair of oxidative damage from normal metabolism can result in an accumulation of defective residues that can contribute to premature cell death by apoptosis. 60,64,[67][68][69] Cockayne syndrome cells respond poorly to oxidative stress. 70 Whether mitochondrial dysfunction plays a role in hearing loss, retinitis pigmentosa, and other manifestations of Cockayne syndrome remains to be determined.…”

Section: Pathophysiologymentioning

confidence: 99%

Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

et al. 2006

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Cockayne syndrome and xeroderma pigmentosum-Cockayne syndrome complex are rare autosomal recessive disorders with poorly understood biology. They are characterized by profound postnatal brain and somatic growth failure and by degeneration of multiple tissues resulting in cachexia, dementia, and premature aging. They result in premature death, usually in childhood, exceptionally in adults. This study compares the clinical course and pathology of a man with Cockayne syndrome group A who died at age 31½ years with 15 adequately documented other adults with Cockayne syndrome and 5 with xeroderma pigmentosum-Cockayne syndrome complex. Slowing of head and somatic growth was apparent before age 2 years, mental retardation and slowly progressive spasticity at 4 years, ataxia and hearing loss at 9 years, visual impairment at 14 years, typical Cockayne facies at 17 years, and cachexia and dementia in his twenties, with a retained outgoing personality. He experienced several transient right and left hemipareses and two episodes of status epilepticus following falls. Neuropathology disclosed profound microencephaly, bilateral old subdural hematomas, white-matter atrophy, tigroid leukodystrophy with string vessels, oligodendrocyte proliferation, bizarre reactive astrocytes, multifocal dystrophic calcification that was most marked in the basal ganglia, advanced atherosclerosis, mixed demyelinating and axonal neuropathy, and neurogenic muscular atrophy. Cellular degeneration of the organ of Corti, spiral and vestibular ganglia, and all chambers of the eye was severe. Rarely, and for unexplained reasons, in some patients with Cockayne syndrome the course is slower than usual, resulting in survival into adulthood. The profound dwarfing, failure of brain growth, cachexia, selectivity of tissue degeneration, and poor correlation between genotypes and phenotypes are not understood. Deficient repair of DNA can increase vulnerability to oxidative stress and play a role in the premature aging, but why patients with mutations in xeroderma pigmentosum genes present with the Cockayne syndrome phenotype is still not known.

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Section: Pathophysiologymentioning

confidence: 99%

Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

et al. 2006

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“…NER removes a wide range of DNA helix-distorting injuries, including ultraviolet light (UV)-induced lesions 6 . TCR is a repair pathway that eliminates both classical NER lesions and oxidative DNA injuries from the transcribed strand 7,8 . Photosensitive features of xeroderma pigmentosum are caused by defective NER, whereas features of Cockayne syndrome and TTD are attributed to defective TCR and transcription function.…”

mentioning

confidence: 99%

A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A

et al. 2004

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“…In support of this hypothesis, we have found that while both CS-B and UV S S cells are defective in host-cell reactivation (HCR) of UV-irradiated shuttle vectors, only CS cells exhibit defective HCR of vectors containing the oxidized bases thymine glycol (Tg) or 8-oxoG; we also found that CS-A and CS-B cells exhibit enhanced sensitivity to treatment with hydrogen peroxide (H 2 O 2 ), while UV S S cells behave like wild type cells in that regard [17]. Previous reports claiming to document TCR of oxidative DNA lesions in wild type human cells, and the absence of that pathway in CS cells, have been retracted [18][19][20][21]. To date there is no direct biochemical evidence for the existence of a dedicated mechanism for removal of oxidative lesions from DNA strands that are templates for transcription.…”

Section: Repair Deficient Diseasesmentioning

confidence: 82%

New applications of the Comet assay: Comet–FISH and transcription-coupled DNA repair

Spivak

Cox

Hanawalt

2009

Mutation Research/Reviews in Mutation Research

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Transcription-coupled repair (TCR) is a pathway dedicated to the removal of damage from the template strands of actively transcribed genes. Although the detailed mechanism of TCR is not yet understood, it is believed to be triggered when a translocating RNA polymerase is arrested at a lesion or unusual structure in the DNA. Conventional assays for TCR require high doses of DNA damage for the statistical analysis of repair in the individual strands of DNA sequences ranging in size from a few hundred bases to 30 kb. The single cell gel electrophoresis (Comet) assay allows detection of single-or double-strand breaks at a 10 to 100-fold higher level of resolution. Fluorescence in situ hybridization (FISH) combined with the Comet assay (Comet-FISH) affords a heightened level of sensitivity for the assessment of repair in defined DNA sequences of cells treated with physiologically relevant doses of genotoxins. This approach also reveals localized susceptibility to chromosomal breakage in cells from individuals with hypersensitivity to radiation or chemotherapy. Several groups have reported preferential repair in transcriptionally active genes or chromosomal domains using Comet-FISH. The prevailing interpretation of the behavior of DNA in the Comet assay assumes that the DNA is arranged in loops and matrix-attachment sites; that supercoiled, undamaged loops are contained within the nuclear matrix and appear in Comet "heads", and that Comet "tails" consist of relaxed DNA loops containing one or more breaks. According to this model, localization of FISH probes in Comet heads signifies that loops containing the targeted sequences are free of damage. This implies that preferential repair as detected by Comet-FISH might encompass large chromosomal domains containing both transcribed and non-transcribed sequences. We review the existing evidence and discuss the implications in relation to current models for the molecular mechanism of TCR.

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Transcription-Coupled Repair of 8-oxoguanine: Requirement for XPG, TFIIH, and CSB and Implications for Cockayne Syndrome

Cited by 143 publications

References 0 publications

Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A

New applications of the Comet assay: Comet–FISH and transcription-coupled DNA repair

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