Ultraviolet radiation alters the phosphorylation of RNA polymerase II large subunit and accelerates its proteasome-dependent degradation

Luo, Zhonghui; Ji, Zheng; Lu, Yi; Bregman, David B.

doi:10.1016/s0921-8777(01)00097-0

Cited by 68 publications

(57 citation statements)

References 44 publications

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“…We wanted to find out whether there is any biological condition inducing this type of cell death. As reported previously (16), exposure of HCT116 cells to a high dose of UV radiation (30 J/m 2 ) induced the ubiquitin-mediated degradation of pol II LS, resulting in transcriptional blockade and apoptosis 24 h after the treatment (Fig. 7D, right panel).…”

Section: Fig 5 Treatment With ␣-Amanitin Induces G 1 -S Transition supporting

confidence: 82%

“…Biological Significance of p53-mediated Apoptosis Induced by Transcriptional Blockade-The induction of DNA lesions by high doses of UV radiation results in the ubiquitination and degradation of pol II LS, transcriptional collapse, and recruitment of DNA repair proteins (16,17). Prolonged inhibition of transcription as a result of a failure to repair such DNA lesions results in cell death by apoptosis (18).…”

Section: Cells Treated With ␣-Amanitin Undergo Apoptosis On Entry Intmentioning

confidence: 99%

“…Lesions in the transcribed strand of DNA induced by high concentrations of chemotherapeutic agents such as cisplatin or by high doses of UV radiation trigger the ubiquitination and consequent degradation of the large subunit (LS) 1 of RNA polymerase II (pol II), resulting in transcriptional collapse and the recruitment of DNA repair proteins (16,17). A prolonged blockage of pol II-dependent transcription caused by failure to repair such DNA lesions results in cell death by apoptosis (18).…”

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confidence: 99%

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Transcriptional Blockade Induces p53-dependent Apoptosis Associated with Translocation of p53 to Mitochondria

Arima

Nitta

Kuninaka

et al. 2005

Journal of Biological Chemistry

139

145

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The tumor suppressor p53 functions as a transcriptional activator to induce cell cycle arrest and apoptosis in response to DNA damage. Although p53 was also shown to mediate apoptosis in a manner independent of its transactivation activity, the mechanism and conditions that trigger such cell death have remained largely unknown. We have now shown that inhibition of RNA polymerase II-mediated transcription by ␣-amanitin or RNA interference induced p53-dependent apoptosis. Inhibition of pol II-mediated transcription resulted in down-regulation of p21 Cip1 , which was caused by both transcriptional suppression and protein degradation, despite eliciting p53 accumulation, allowing the cells to progress into S phase and then to undergo apoptosis. This cell death did not require the transcription of p53 target genes and was preceded by translocation of the accumulated p53 to mitochondria. Our data thus suggested that blockade of pol II-mediated transcription induced p53 accumulation in mitochondria and was the critical factor for eliciting p53-dependent but transcription-independent apoptosis.

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Section: Fig 5 Treatment With ␣-Amanitin Induces G 1 -S Transition supporting

confidence: 82%

Section: Cells Treated With ␣-Amanitin Undergo Apoptosis On Entry Intmentioning

confidence: 99%

mentioning

confidence: 99%

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Transcriptional Blockade Induces p53-dependent Apoptosis Associated with Translocation of p53 to Mitochondria

Arima

Nitta

Kuninaka

et al. 2005

Journal of Biological Chemistry

139

145

View full text Add to dashboard Cite

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“…This effect can be partially overcome by microinjecting TATA-binding protein into UVtreated fibroblasts (159). UV light also leads to a shift in the proportion of the hypophosphorylated (IIo) and hyperphosphorylated (IIa) forms of the largest subunit of RNA polymerase II (91,105,133). The net effect is a decrease of the IIo form with a corresponding increase in the IIa form (91,105,133).…”

Section: Introductionmentioning

confidence: 99%

“…UV light also leads to a shift in the proportion of the hypophosphorylated (IIo) and hyperphosphorylated (IIa) forms of the largest subunit of RNA polymerase II (91,105,133). The net effect is a decrease of the IIo form with a corresponding increase in the IIa form (91,105,133). It has been suggested that the depletion of the initiating IIo form contributes to UV-induced inhibition of transcription (133).…”

Section: Introductionmentioning

confidence: 99%

Post-Transcriptional Regulation of DNA Damage-Responsive Gene Expression

McKay

2014

Antioxidants & Redox Signaling

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Significance: Production of proteins requires the synthesis, maturation, and export of mRNAs before their translation in the cytoplasm. Endogenous and exogenous sources of DNA damage pose a challenge to the coordinated regulation of gene expression, because the integrity of the DNA template can be compromised by DNA lesions. Cells recognize and respond to this DNA damage through a variety of DNA damage responses (DDRs). Failure to deal with DNA damage appropriately can lead to genomic instability and cancer. Recent Advances: The p53 tumor suppressor plays a dominant role in DDR-dependent changes in gene expression, but this transcription factor is not solely responsible for all changes. Recent evidence indicates that RNA metabolism is integral to DDRs as well. In particular, post-transcriptional processes are emerging as important contributors to these complex responses. Critical Issues: Transcriptional, post-transcriptional, and translational regulation of gene expression is subject to changes in response to DNA damage. How these processes are intertwined in the unfolding of DDR is not fully understood. Future Directions: Many complex regulatory responses combine to determine cell fate after DNA damage. Understanding how transcriptional, post-transcriptional, and translational processes interdigitate to create a web of regulatory interactions will be one of the key challenges to fully understand DDRs. Antioxid. Redox Signal. 20, 640-654.

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An insight into the abundant proteome of 46BR.1G1 fibroblasts deficient of DNA ligase I

Giuliano

Iadarola

Leva³

et al. 2012

Electrophoresis

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This work presents the proteome profile of cultured human skin fibroblasts established from a patient affected by DNA ligase I (Lig I) deficiency syndrome, a rare disorder characterized by immunodeficiency, growth retardation and sun sensitivity. 2-DE (in the 3-10 and 4-7 pH ranges) was the separation technique used for the production of maps. MALDI-TOF/MS and LC-MS/MS were the mass spectrometry platforms applied for the identification of proteins in gel spots. A total of 154 proteins, including 41 never detected before in skin fibroblasts with this approach, were identified in gel spots analyzed. This newly generated extensive database provides for the first time a global picture of abundant proteins in 46BR.1G1 skin fibroblasts. While being relevant to the particular disorder considered, these results may be regarded as an intriguing starting point on the way to achieve a reference map of the proteins highly expressed in an inherited syndrome with defect in DNA replication and repair pathways.

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Ultraviolet radiation alters the phosphorylation of RNA polymerase II large subunit and accelerates its proteasome-dependent degradation

Cited by 68 publications

References 44 publications

Transcriptional Blockade Induces p53-dependent Apoptosis Associated with Translocation of p53 to Mitochondria

Transcriptional Blockade Induces p53-dependent Apoptosis Associated with Translocation of p53 to Mitochondria

Post-Transcriptional Regulation of DNA Damage-Responsive Gene Expression

An insight into the abundant proteome of 46BR.1G1 fibroblasts deficient of DNA ligase I

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