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

239 Scopus citations

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

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this