The role of BRCA1 in transcriptional regulation and cell cycle control.
The exact functions of BRCA1 have not been fully described but it now seems apparent that it has roles in DNA damage repair, transcriptional regulation, cell cycle control and most recently in ubiquitylation. These functions of BRCA1 are most likely interdependent but this review will focus on the role of BRCA1 in relation to transcriptional regulation and in particular how this impacts upon cell cycle control. We will (i) describe the structure of BRCA1 and how it may contribute to its transcription function; (ii) describe the interaction of BRCA1 with the core transcriptional machinery (RNA polII); (iii) describe how BRCA1 may regulate transcription at an epigenetic level through chromatin modification; (iv) discuss the role of BRCA1 in modulating transcription through its association with sequence-specific transcription factors. Finally, we will discuss the possible effects of BRCA1 transcriptional regulation on downstream targets with known roles in cell cycle control.
Mullan
P B
PB
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Lisburn Road Belfast, Northern Ireland, UK.
Quinn
J E
JE
Harkin
D P
DP
D019313:BRCA1 Protein / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008938:Mitosis / Q000235:genetics; D012320:RNA Polymerase III / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019313:BRCA1 Protein; D002843:Chromatin; D016160:Retinoblastoma Protein; D050794:STAT1 Transcription Factor; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D012320:RNA Polymerase III