The identification of a novel role for BRCA1 in regulating RNA Polymerase I transcription

Rebecca Johnston, Zenobia D'Costa, Swagat Ray, Julia Gorski, D. Paul Harkin, Paul Mullan, Konstantin I. Panov

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.
LanguageEnglish
Number of pages14
JournalOncotarget
DOIs
Publication statusPublished - 31 Aug 2016

Fingerprint

DNA Damage
Ribosomal DNA
Ribosomes
Holoenzymes
Nucleic Acid Regulatory Sequences
Ubiquitination
Phosphoproteins
Cell Cycle Checkpoints
rRNA Genes
Cell Proliferation
Neoplasms

Cite this

@article{bd6ff59f50dd4f0e98adf519a2175168,
title = "The identification of a novel role for BRCA1 in regulating RNA Polymerase I transcription",
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.",
author = "Rebecca Johnston and Zenobia D'Costa and Swagat Ray and Julia Gorski and Harkin, {D. Paul} and Paul Mullan and Panov, {Konstantin I.}",
year = "2016",
month = "8",
day = "31",
doi = "10.18632/oncotarget.11770",
language = "English",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",

}

The identification of a novel role for BRCA1 in regulating RNA Polymerase I transcription. / Johnston, Rebecca; D'Costa, Zenobia; Ray, Swagat; Gorski, Julia; Harkin, D. Paul; Mullan, Paul; Panov, Konstantin I.

In: Oncotarget, 31.08.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The identification of a novel role for BRCA1 in regulating RNA Polymerase I transcription

AU - Johnston, Rebecca

AU - D'Costa, Zenobia

AU - Ray, Swagat

AU - Gorski, Julia

AU - Harkin, D. Paul

AU - Mullan, Paul

AU - Panov, Konstantin I.

PY - 2016/8/31

Y1 - 2016/8/31

N2 - 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.

AB - 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.

U2 - 10.18632/oncotarget.11770

DO - 10.18632/oncotarget.11770

M3 - Article

JO - Oncotarget

T2 - Oncotarget

JF - Oncotarget

SN - 1949-2553

ER -