Cockayne syndrome group B protein enhances elongation  by RNA polymerase II

Selby, Christopher P.; Sancar, Aziz

doi:10.1073/pnas.94.21.11205

Cited by 282 publications

(201 citation statements)

References 35 publications

Supporting

Mentioning

186

Contrasting

Unclassified

Order By: Relevance

“…Besides the defect in coping with many types of DNA damaging agents, CSB cells have markedly reduced transcription (Balajee et al, 1997;Dianov et al, 1997). CSB stimulates transcription by stimulating elongation of actively transcribing RNA polymerase bound to DNA and nascent RNA (Selby and Sancar, 1997a;Tantin et al, 1997;. Furthermore, using array analysis, Kyng et al (Kyng et al, 2003) demonstrated that the transcriptional response after oxidative stress is defective in CSB cells.…”

Section: The Role Of Csb In Various Cellular Processesmentioning

confidence: 99%

“…In vivo transcription in CSB deficient cells have been reported to be 50% of wild type cells and in vitro transcription studies on chromatin from CSB deficient cells found that transcription elongation was significantly decreased in the absence of CSB (Selby and Sancar, 1997a). When compared to CSB deficient cells, the transcription from chromatin in wild type cells was more resistant to the detergent Triton X-100, indicating that the transcription machinery is less tightly associated with chromatin in CSB deficient cells compared to wild type cells (Balajee et al, 1997).…”

Section: Csb and Chromatin Structurementioning

confidence: 99%

See 1 more Smart Citation

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

126

View full text Add to dashboard Cite

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.

show abstract

Section: The Role Of Csb In Various Cellular Processesmentioning

confidence: 99%

Section: Csb and Chromatin Structurementioning

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

126

View full text Add to dashboard Cite

show abstract

“…Rather, it appears that the severe photoreceptor loss in Csb m/m animals represents a CS-specific trait related to a function of the CSB protein outside the context of NER. The nature of this non-NER function is not yet clear, but there are indications that the CSB protein has an auxiliary function in transcription elongation, notably the bypass of pause sites and RNA secondary structures (3,18,30,42), as well as in the repair of other (non-NER-type) oxidative DNA lesions (16,17,39,43 (43) recently showed that plasmids containing 8-oxoG are less well repaired by CS patient cells, whereas strand breaks (as also produced by ionizing radiation) are repaired at a normal rate. Furthermore, Csb m/m mice are sensitive to the pro-oxidant di-(2-ethylhexyl)phthalate, and exposed animals contain higher levels of 8-oxoG in the liver than wt mice (15,16).…”

Section: Discussionmentioning

confidence: 99%

“…The CS-specific features may be attributed to other roles of CSA and CSB proteins, outside the context of NER. There are indications that these proteins are involved in transcription elongation (3,18,30,42) and in the repair of other, non-NER types of DNA damage, e.g., oxidative DNA lesions (15-17, 39, 43, 45).…”

mentioning

confidence: 99%

Retinal Degeneration and Ionizing Radiation Hypersensitivity in a Mouse Model for Cockayne Syndrome

Gorgels

Pluijm

Brandt

et al. 2007

Molecular and Cellular Biology

View full text Add to dashboard Cite

Mutations in the CSB gene cause Cockayne syndrome (CS), a DNA repair disorder characterized by UV sensitivity and severe physical and neurological impairment. CSB functions in the transcription-coupled repair subpathway of nucleotide excision repair. This function may explain the UV sensitivity but hardly clarifies the other CS symptoms. Many of these, including retinopathy, are associated with premature aging. We studied eye pathology in a mouse model for CS. Csb m/m mice were hypersensitive to UV light and developed epithelial hyperplasia and squamous cell carcinomas in the cornea, which underscores the importance of transcriptioncoupled repair of photolesions in the mouse. In addition, we observed a spontaneous loss of retinal photoreceptor cells with age in the Csb m/m retina, resulting in a 60% decrease in the number of rods by the age of 18 months. Importantly, when Csb m/m mice (as well as Csa ؊/؊ mice) were exposed to 10 Gy of ionizing radiation, we noticed an increase in apoptotic photoreceptor cells, which was not observed in wild-type animals. This finding, together with our observation that the expression of established oxidative stress marker genes is upregulated in the Csb m/m retina, suggests that (endogenous) oxidative DNA lesions play a role in this CS-specific premature-aging feature and supports the oxidative DNA damage theory of aging.

show abstract

“…The first class is composed of members of the SII family. 3,5 The second class comprises a collection of elongation factors, including TFIIF, 6 Elongin, 7,8 ELL 9 and CSB, 10 which increase the overall rate of mRNA chain elongation by decreasing the frequency and/or duration of transient pausing of pol II at sites along the DNA template.…”

mentioning

confidence: 99%

Induction of apoptosis and cellular senescence in mice lacking transcription elongation factor, Elongin A

et al. 2006

View full text Add to dashboard Cite

Elongin A is a transcription elongation factor that increases the overall rate of mRNA chain elongation by RNA polymerase II. To gain more insight into the physiological functions of Elongin A, we generated Elongin A-deficient mice. Elongin A homozygous mutant (Elongin A À/À ) embryos demonstrated a severely retarded development and died at between days 10.5 and 12.5 of gestation, most likely due to extensive apoptosis. Moreover, mouse embryonic fibroblasts (MEFs) derived from Elongin A À/À embryos exhibited not only increased apoptosis but also senescence-like growth defects accompanied by the activation of p38 MAPK and p53. Knockdown of Elongin A in MEFs by RNA interference also dramatically induced the senescent phenotype. A study using inhibitors of p38 MAPK and p53 and the generation of Elongin A-deficient mice with p53-null background suggests that both the p38 MAPK and p53 pathways are responsible for the induction of senescence-like phenotypes, whereas additional signaling pathways appear to be involved in the mediation of apoptosis in Elongin A À/À cells. Taken together, our results suggest that Elongin A is required for the transcription of genes essential for early embryonic development and downregulation of its activity is tightly associated with cellular senescence. Cell Death and Differentiation (2007) Eukaryotic mRNA synthesis by RNA polymerase II (pol II) is regulated by the concerted action of a set of transcription factors that control the activity of pol II during the initiation and elongation stages of transcription. At least six general transcription factors have been identified in eukaryotic cells and found to promote the selective binding of pol II to promoters and to support the basal level of transcription. 1 In addition, a diverse collection of elongation factors that promote efficient elongation of transcripts by pol II in vitro have also been identified. 2-4 These factors fall into two broad functional classes based on their ability to either reactivate arrested pol II or suppress the transient pausing of pol II. The first class is composed of members of the SII family. 3,5 The second class comprises a collection of elongation factors, including TFIIF, 6 Elongin, 7,8 ELL 9 and CSB, 10 which increase the overall rate of mRNA chain elongation by decreasing the frequency and/or duration of transient pausing of pol II at sites along the DNA template.Elongin was identified as a heterotrimer composed of A, B and C subunits of B770, 118 and 112 amino acids, respectively. 7,8,11,12 Elongin A is the transcriptionally active subunit, whereas Elongins B and C are positive regulatory subunits that can form an isolable Elongin BC subcomplex. 8,13,14 Although the functions of Elongin A in vivo remain largely unclear, Gerber et al. 15 have recently reported that the Drosophila homolog of Elongin A (dEloA) colocalizes with pol II at sites of active transcription on polytene chromosomes, and it also plays a critical role in heat shock gene expression in vivo. 15,16 Moreover, by the RNA interference (...

show abstract

Cockayne syndrome group B protein enhances elongation by RNA polymerase II

Cited by 282 publications

References 35 publications

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

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

Retinal Degeneration and Ionizing Radiation Hypersensitivity in a Mouse Model for Cockayne Syndrome

Induction of apoptosis and cellular senescence in mice lacking transcription elongation factor, Elongin A

Contact Info

Product

Resources

About