Abstract
The unrestrained proliferation of cancer cells requires a high level of ribosome
biogenesis. The first stage of ribosome biogenesis is the transcription of the large
ribosomal RNAs (rRNAs); the structural and functional components of the ribosome.
Transcription of rRNA is carried out by RNA Polymerase I (Pol-I) and its associated
holoenzyme complex.
Here we report that BRCA1, a nuclear phosphoprotein, and a known tumour
suppressor involved in variety of cellular processes such as DNA damage response,
transcriptional regulation, cell cycle control and ubiquitylation, is associated with
rDNA repeats, in particular with the regulatory regions of the rRNA gene.
We demonstrate that BRCA1 interacts directly with the basal Pol-I transcription
factors; upstream binding factor (UBF), selectivity factor-1 (SL1) as well as interacting
with RNA Pol-I itself. We show that in response to DNA damage, BRCA1 occupancy
at the rDNA repeat is decreased and the observed BRCA1 interactions with the Pol-I
transcription machinery are weakened.
We propose, therefore, that there is a rDNA associated fraction of BRCA1 involved
in DNA damage dependent regulation of Pol-I transcription, regulating the stability
and formation of the Pol-I holoenzyme during initiation and/or elongation in response
to DNA damage.
Original language | English |
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Number of pages | 14 |
Journal | Oncotarget |
DOIs | |
Publication status | Published - 31 Aug 2016 |
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Konstantin Panov
- School of Biological Sciences - Senior Lecturer
- Institute for Global Food Security
Person: Academic