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DNA Damage Induced Inhibition of RNA Polymerase II and the Contributions of BRCA1
Author(s) -
Heine George F,
Horwitz Andrew A,
Parvin Jeffrey D
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.821.1
Subject(s) - rna polymerase ii , transcription (linguistics) , dna damage , ubiquitin , microbiology and biotechnology , dna repair , phosphorylation , chemistry , dna , psychological repression , polymerase , biology , gene expression , promoter , gene , biochemistry , linguistics , philosophy
Cellular DNA damage elicits the phosphorylation and ubiquitination of RNA polymerase (RNAPII), leading to the global repression of transcription. Here we show that there are at least two different pathways to transcriptional repression, depending on the type of DNA damage. After H2O2 treatment, transcription was rapidly inhibited and rapidly restored. On the other hand, UV treatment caused a much slower transcriptional inhibition, with a corresponding depletion of unphosphorylated RNAPII. We found that after UV treatment, but not treatment with H2O2, the inhibition of transcription was dependent on both the proteasome and new protein synthesis. In addition, RNAPII activity and ubiquitination were regulated through the phosphorylation of RNAPII by the P‐TEFb kinase. Furthermore, we show that BRCA1 is associated with the ubiquitination of RNAPII in response to UV induced DNA damage. These results highlight that multiple cellular pathways exist to globally repress transcriptional processes that might interfere with the repair of DNA damage.