Ultraviolet radiation-induced ubiquitination and proteasomal degradation of the large subunit of RNA polymerase II: Implications for transcription- coupled DNA repair

Joshua N. Ratner, Bhavani Balasubramanian, Jeffry Corden, Stephen L. Warren, David B. Bregman

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

We have shown previously that UV radiation and other DNA-damaging agents induce the ubiquitination of a portion of the RNA polymerase II large subunit (Pol II LS). In the present study UV irradiation of repaircompetent fibroblasts induced a transient reduction of the Pol II LS level; new protein synthesis restored Pol II LS to the base-line level within 16-24 h. In repair-deficient xeroderma pigmentosum cells, UV radiation-induced ubiquitination of Pol II LS was followed by a sustained reduction of Pol II LS level. In both normal and xeroderma pigmentosum cells, the ubiquitinated Pol II LS had a hyperphosphorylated COOH-terminal domain (CTD), which is characteristic of elongating Pol II. The portion of Pol II LS whose steady- state level diminished most quickly had a relatively hypophosphorylated CTD. The ubiquitinated residues did not map to the CTD. Importantly, UV-induced reduction of Pol II LS level in repair-competent or -deficient cells was inhibited by the proteasome inhibitors lactacystin or MG132. These data demonstrate that UV-induced ubiquitination of Pol H LS is followed by its degradation in the proteasome. These results suggest, contrary to a current model of transcription-coupled DNA repair, that elongating Pol II complexes which arrest at intragenic DNA lesions may be aborted rather than resuming elongation after repair takes place.

Original languageEnglish (US)
Pages (from-to)5184-5189
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number9
DOIs
StatePublished - Feb 27 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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