Reduced RNA polymerase II transcription in intact and permeabilized Cockayne syndrome group B cells

Balajee, Adayabalam S.; May, Alfred; Dianov, Grigory L.; Friedberg, Errol C.; Bohr, Vilhelm A.

doi:10.1073/pnas.94.9.4306

Cited by 157 publications

(103 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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). A study by Weiner and coworkers found that the transcription pattern of CSB deficient cells had a significant overlap with the transcription pattern of cells treated with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA), indicating that CSB could play a role in chromatin maintenance (Newman et al, 2006).…”

Section: Csb and Chromatin Structurementioning

confidence: 97%

“…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;.…”

Section: The Role Of Csb In Various Cellular Processesmentioning

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

Self Cite

124

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: Csb and Chromatin Structurementioning

confidence: 97%

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

Self Cite

124

View full text Add to dashboard Cite

show abstract

“…RNA synthesis RNA synthesis was determined based on a method described previously (Balajee et al, 1997). Approximately 4.0 Â 10 4 cells were plated in 35 mm Petri dishes and 24 h after plating they were treated with TMZ (0.1 mM) and maintained with the drug for the indicated times.…”

Section: Western Blot Analysismentioning

confidence: 99%

Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine

Roos¹,

et al. 2006

View full text Add to dashboard Cite

Methylating drugs such as temozolomide (TMZ) are widely used in the treatment of brain tumours (malignant gliomas). The mechanism of TMZ-induced glioma cell death is unknown. Here, we show that malignant glioma cells undergo apoptosis following treatment with the methylating agents N-methyl-N 0 -nitro-N-nitrosoguanidine (MNNG) and TMZ. Cell death determined by colony formation and apoptosis following methylation is greatly stimulated by p53. Transfection experiments with O 6 -methylguanine-DNA methyltransferase (MGMT) and depletion of MGMT by O 6 -benzylguanine showed that, in gliomas, the apoptotic signal originates from O 6 -methylguanine (O 6 MeG) and that repair of O 6 MeG by MGMT prevents apoptosis. We further demonstrate that O 6 MeGtriggered apoptosis requires Fas/CD95/Apo-1 receptor activation in p53 non-mutated glioma cells, whereas in p53 mutated gliomas the same DNA lesion triggers the mitochondrial apoptotic pathway. This occurs less effectively via Bcl-2 degradation and caspase-9, -2, -7 and -3 activation. O 6 MeG-triggered apoptosis in gliomas is a late response (occurring >120 h after treatment) that requires extensive cell proliferation. Stimulation of cell cycle progression by the Pasteurella multocida toxin promoted apoptosis whereas serum starvation attenuated it. O 6 MeGinduced apoptosis in glioma cells was preceded by the formation of DNA double-strand breaks (DSBs), as measured by cH2AX formation. Glioma cells mutated in DNA-PK cs , which is involved in non-homologous endjoining, were more sensitive to TMZ-induced apoptosis, supporting the involvement of DSBs as a downstream apoptosis triggering lesion. Overall, the data demonstrate that cell death induced by TMZ in gliomas is due to apoptosis and that determinants of sensitivity of gliomas to TMZ are MGMT, p53, proliferation rate and DSB repair.

show abstract

“…The loss of both TCR activity and the ability to resume transcription after damage in CS-B cells illustrates the importance of the CSB gene in the coordinated regulation of both repair and transcription activities. Earlier studies from our laboratory suggested that the elongation mode of RNA polymerase II transcription may be reduced in CS-B cells and that the transcription apparatus in CS cells might be very sensitive to endogenous DNA damage (Balajee et al, 1997;Dianov et al, 1997).…”

Section: Tcr Defect Correlates With Apoptotic Responsementioning

confidence: 99%

“…Besides a role in DNA repair, the CSB protein is involved in basal transcription (Balajee et al, 1997), and interacts with RNA polymerase II (Van Gool et al, 1997). The CSB protein is a DNA-stimulated ATPase, but fails to exhibit DNA unwinding activity as measured by the conven-tional strand displacement assay (Selby and Sancar, 1997;Tantin et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Role of the ATPase domain of the Cockayne syndrome group B protein in UV induced apoptosis

Proietti-De-Santis

et al. 2000

Oncogene

View full text Add to dashboard Cite

Cockayne syndrome (CS) is a human autosomal recessive disorder characterized by many neurological and developmental abnormalities. CS cells are defective in the transcription coupled repair (TCR) pathway that removes DNA damage from the transcribed strand of active genes. The individuals su ering from CS do not generally develop cancer but show increased neurodegeneration. Two genetic complementation groups (CS-A and CS-B) have been identi®ed. The lack of cancer formation in CS may be due to selective elimination of cells containing DNA damage by a suicidal pathway. In this study, we have evaluated the role of the CSB gene in UV induced apoptosis in human and hamster cells. The hamster cell line UV61 carries a mutation in the homolog of the human CSB gene. We show that both human CS-B and hamster UV61 cells display increased apoptotic response following UV exposure compared with normal cells. The increased sensitivity of UV61 cells to apoptosis is complemented by the transfection of the wild type human CSB gene. In order to determine which functional domain of the CSB gene participates in the apoptotic pathway, we constructed stable cell lines with di erent CSB domain disruptions. UV61 cells were stably transfected with the human CSB cDNA containing a point mutation in the highly conserved glutamic acid residue in ATPase motif II. This cell line (UV61/ pc3.1-CSBE646Q) showed the same increased apoptosis as the UV61 cells. In contrast, cells containing a deletion in the acidic domain at the N-terminal end of the CSB protein had no e ect on apoptosis. This indicates that the integrity of the ATPase domain of CSB protein is critical for preventing the UV induced apoptotic pathway. In primary human CS-B cells, the induction and stabilization of the p53 protein seems to correlate with their increased apoptotic potential. In contrast, no change in the level of either p53 or activation of mdm2 protein by p53 was observed in hamster UV61 cells after UV exposure. This suggests that the CSB dependent apoptotic pathway can occur independently of the transactivation potential of p53 in hamster cells.

show abstract

Reduced RNA polymerase II transcription in intact and permeabilized Cockayne syndrome group B cells

Cited by 157 publications

References 41 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

Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine

Role of the ATPase domain of the Cockayne syndrome group B protein in UV induced apoptosis

Contact Info

Product

Resources

About