UV-induced ubiquitination of RNA polymerase II

A novel modification deficient in Cockayne syndrome cells

David B. Bregman, Ruth Halaban, Alain J. Van Gool, Karla A. Henning, Errol C. Friedberg, Stephen L. Warren

Research output: Contribution to journalArticle

234 Citations (Scopus)

Abstract

Damage to actively transcribed DNA is preferentially repaired by the transcription-coupled repair (TCR) system. TCR requires RNA polymerase II (Pol II), but the mechanism by which repair enzymes preferentially recognize and repair DNA lesions on Pol II-transcribed genes is incompletely understood. Herein we demonstrate that a fraction of the large subunit of Pol II (Pol II LS) is ubiquitinated after exposing cells to UV-radiation or cisplatin but not several other DNA damaging agents. This novel covalent modification of Pol II LS occurs within 15 min of exposing cells to UV- radiation and persists for about 8-12 hr. Ubiquitinated Pol II LS is also phosphorylated on the C-terminal domain. UV-induced ubiquitination of Pol II LS is deficient in fibroblasts from individuals with two forms of Cockayne syndrome (CS-A and CS-B), a rare disorder in which TCR is disrupted. UV- induced ubiquitination of Pol II LS can be restored by introducing cDNA constructs encoding the CSA or CSB genes, respectively, into CS-A or CS-B fibroblasts. These results suggest that ubiquitination of Pol II LS plays a role in the recognition and/or repair of damage to actively transcribed genes. Alternatively, these findings may reflect a rule played by the CSA and CSB gene products in transcription.

Original languageEnglish (US)
Pages (from-to)11586-11590
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number21
DOIs
StatePublished - Oct 15 1996

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Cockayne Syndrome
RNA Polymerase II
Ubiquitination
Genes
Fibroblasts
Radiation
DNA
DNA Repair
Cisplatin
Complementary DNA
Enzymes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

UV-induced ubiquitination of RNA polymerase II : A novel modification deficient in Cockayne syndrome cells. / Bregman, David B.; Halaban, Ruth; Van Gool, Alain J.; Henning, Karla A.; Friedberg, Errol C.; Warren, Stephen L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 21, 15.10.1996, p. 11586-11590.

Research output: Contribution to journalArticle

Bregman, David B. ; Halaban, Ruth ; Van Gool, Alain J. ; Henning, Karla A. ; Friedberg, Errol C. ; Warren, Stephen L. / UV-induced ubiquitination of RNA polymerase II : A novel modification deficient in Cockayne syndrome cells. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 21. pp. 11586-11590.
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