Cockayne syndrome B protein regulates the transcriptional program after UV irradiation

Proietti-De-Santis, Luca; Drané, Pascal; Egly, Jean‐Marc

doi:10.1038/sj.emboj.7601071

Cited by 142 publications

(145 citation statements)

References 33 publications

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“…It has been hypothesized that CSB would induce transcription of genes encoding DNA glycosylases such as OGG1 (Dianov et al, 1999;Tuo et al, 2002). Suggestion of a defect in the transcriptional response of CS-B cells after H 2 O 2 treatment has been provided (Kyng et al, 2003) and a recent study demonstrates that CSB is involved in the regulation of the transcriptional program after UV damage (Proietti-De-Santis et al, 2006). It would be interesting to analyse further the role of CS proteins in transcription regulation after oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

The role of CSA in the response to oxidative DNA damage in human cells

et al. 2007

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Cockayne syndrome (CS) is a rare genetic disease characterized by severe growth, mental retardation and pronounced cachexia. CS is most frequently due to mutations in either of two genes, CSB and CSA. Evidence for a role of CSB protein in the repair of oxidative DNA damage has been provided recently. Here, we show that CSA is also involved in the response to oxidative stress. CS-A human primary fibroblasts and keratinocytes showed hypersensitivity to potassium bromate, a specific inducer of oxidative damage. This was associated with inefficient repair of oxidatively induced DNA lesions, namely 8-hydroxyguanine (8-OH-Gua) and (5 0 S)-8,5 0 -cyclo 2 0 -deoxyadenosine. Expression of the wild-type CSA in the CS-A cell line CS3BE significantly decreased the steady-state level of 8-OH-Gua and increased its repair rate following oxidant treatment. CS-A cell extracts showed normal 8-OH-Gua cleavage activity in an in vitro assay, whereas CS-B cell extracts were confirmed to be defective. Our data provide the first in vivo evidence that CSA protein contributes to prevent accumulation of various oxidized DNA bases and underline specific functions of CSB not shared with CSA. These findings support the hypothesis that defective repair of oxidative DNA damage is involved in the clinical features of CS patients.

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Section: Discussionmentioning

confidence: 99%

The role of CSA in the response to oxidative DNA damage in human cells

et al. 2007

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“…This phenomenon was not observed for p53 responsive genes indicating that these genes can be transcribed in the absence of CSB. The role of CSB in initiation of housekeeping genes after UV could be related to CSB-mediated chromatin remodelling events facilitating the recruitment of TBP and other factors to promoters after UV irradiation [37]. These data together indicate that transcription inhibition and recovery is unlikely to be governed by a single mechanism.…”

Section: Tc-ner and Transcription Response: A Complex Relationshipmentioning

confidence: 93%

“…When added to a stalled RNAPIIo (at a CPD photolesion) CSB can stimulate transcription elongation by addition of one nucleotide to the nascent transcript, but not bypass of the lesion [36]. In addition, CSB plays a role in initiating the transcriptional program of a subset of genes after UV-irradiation [37]. It is conceivable that these features may underlie some aspects of the complex clinical phenotype of CS patients.…”

Section: Transcription-coupled Nucleotide Excision Repair Requires Spmentioning

confidence: 99%

“…In vitro transcription assays revealed that transcription initiation is persistently inhibited in extracts of UV-irradiated CS-B cells due to depletion of the transcription initiating RNA polymerase IIa (RNAPIIa) [59]. Proietti-De-Sanctis et al showed a defective reinitiation of transcription of housekeeping genes in CS-B cells due to impairment of transcription initiation complex formation [37]. This phenomenon was not observed for p53 responsive genes indicating that these genes can be transcribed in the absence of CSB.…”

Section: Tc-ner and Transcription Response: A Complex Relationshipmentioning

confidence: 99%

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

2008

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The encounter of elongating RNA polymerase II (RNAPIIo) with DNA lesions has severe consequences for the cell as this event provides a strong signal for P53-dependent apoptosis and cell cycle arrest. To counteract prolonged blockage of transcription, the cell removes the RNAPIIo-blocking DNA lesions by transcription-coupled repair (TC-NER), a specialized subpathway of nucleotide excision repair (NER). Exposure of mice to UVB light or chemicals has elucidated that TC-NER is a critical survival pathway protecting against acute toxic and long-term effects (cancer) of genotoxic exposure. Deficiency in TC-NER is associated with mutations in the CSA and CSB genes giving rise to the rare human disorder Cockayne syndrome (CS). Recent data suggest that CSA and CSB play differential roles in mammalian TC-NER: CSB as a repair coupling factor to attract NER proteins, chromatin remodellers and the CSA-E3-ubiquitin ligase complex to the stalled RNAPIIo. CSA is dispensable for attraction of NER proteins, yet in cooperation with CSB is required to recruit XAB2, the nucleosomal binding protein HMGN1 and TFIIS. The emerging picture of TC-NER is complex: repair of transcription-blocking lesions occurs without displacement of the DNA damage-stalled RNAPIIo, and requires at least two essential assembly factors (CSA and CSB), the core NER factors (except for XPC-RAD23B), and TC-NER specific factors. These and yet unidentified proteins will accomplish not only efficient repair of transcription-blocking lesions, but are also likely to contribute to DNA damage signalling events.

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“…The similarity of HDAC inhibited cells to CSB deficient cells indicates that a role of CSB is to decrease the amount of histone acetylation. In contrast, the acetylation of histone H4 near certain promoters is decreased in CSB deficient cells before and/or after UV irradiation, indicating CSB dependent histone acetylase (HAT) activity, as argued by Egly and coworkers (Proietti-De-Santis et al, 2006). Hence, studies indicate that the chromatin pattern of CSB deficient cells is affected, but it is not clear whether CSB is involved in increasing or decreasing the histone acetylation.…”

Section: Csb and Chromatin Structurementioning

confidence: 95%

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

124

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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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Cockayne syndrome B protein regulates the transcriptional program after UV irradiation

Cited by 142 publications

References 33 publications

The role of CSA in the response to oxidative DNA damage in human cells

The role of CSA in the response to oxidative DNA damage in human cells

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

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

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