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 language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology