UV-induced ubiquitination of RNA polymerase II is deficient in cockayne's syndrome cells

D. B. Bregman, R. Halaban, K. A. Henning, E. C. Friedberg, S. L. Warren

Research output: Contribution to journalArticle

Abstract

Multiple DNA repair mechanisms help cells to avoid neoplastic transformation. Damage to actively transcribed genes is preferentially repaired via the transcription-coupled nucleotide excision repair (tcNEE) system which requires RNA polymerase 11 (Pol II), the polymerase which transcribes protein encoding genes. Nevertheless, the mechanism whereby elongating Pol II recognizes and/or helps repair lesions on transcribed genes remains unknown. Here we demonstrate that the large subunit of Pol II (Pol II LS) becomes ubiquitinated within 15 minutes of exposing cells to ultraviolet (UV) radiation. Cisplatin, which also causes DNA lesions repaired by NER, induces ubiquitination of Pol II LS as well. Moreover, UV-induced ubiquitination of Pol II LS is deficient in fibroblasts from individuals with two forms of Cockayne's syndrome (CSA and CSB), a rare disorder in which tcNER is disrupted. UV-induced ubiquitination of Pol II LS (as well as tcNER) can be restored by introducing cDNA constructs encoding the CSA or CSB genes, respectively, into CSA or CSB fibroblasts. Thus UVinduced ubiquitination of Pol II LS depends upon a functional tcNER svstem. Future studies will address the mechanistic role of this modification.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996

Fingerprint

Cockayne Syndrome
RNA Polymerase II
Ubiquitination
DNA-directed RNA polymerase
Repair
Genes
Fibroblasts
DNA repair
DNA Repair
fibroblasts
Gene encoding
genes
DNA
cells
DNA-Directed RNA Polymerases
Transcription
Ultraviolet radiation
Cisplatin
cisplatin
Nucleotides

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Bregman, D. B., Halaban, R., Henning, K. A., Friedberg, E. C., & Warren, S. L. (1996). UV-induced ubiquitination of RNA polymerase II is deficient in cockayne's syndrome cells. FASEB Journal, 10(6).

UV-induced ubiquitination of RNA polymerase II is deficient in cockayne's syndrome cells. / Bregman, D. B.; Halaban, R.; Henning, K. A.; Friedberg, E. C.; Warren, S. L.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

Bregman, D. B. ; Halaban, R. ; Henning, K. A. ; Friedberg, E. C. ; Warren, S. L. / UV-induced ubiquitination of RNA polymerase II is deficient in cockayne's syndrome cells. In: FASEB Journal. 1996 ; Vol. 10, No. 6.
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