Role played by BRCA1 in regulating the cellular response to stress.
BRCA1 (breast-cancer susceptibility gene 1) is a tumour suppressor gene that is mutated in the germline of women with a genetic predisposition to breast and ovarian cancer. In this review, we examine the role played by BRCA1 in mediating the cellular response to stress. We review the role played by BRCA1 in detecting and signalling the presence of DNA damage, particularly double-strand DNA breaks, and look at the evidence to support a role for BRCA1 in regulating stress response pathways such as the c-Jun N-terminal kinase/stress-activated protein kinase pathway. In addition, we examine the role played by BRCA1 in mediating both cell-cycle arrest and apoptosis following different types of cellular insult, and how this may be modulated by the presence or absence of associated proteins such as p53. Finally, we explore the possibility that many of the functions associated with BRCA1 may be based on transcriptional regulation of key downstream genes that have been implicated in the regulation of these specific cellular pathways.
Gilmore
P M
PM
Cancer Research Centre, Department of Oncology, Queen's University Belfast, University Floor, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK.
Quinn
J E
JE
Mullan
P B
PB
Andrews
H N
HN
McCabe
N
N
Carty
M
M
Kennedy
R D
RD
Harkin
D P
DP
D000818:Animals; D017209:Apoptosis; D019313:BRCA1 Protein / Q000502:physiology*; D015152:Blotting, Northern; D002453:Cell Cycle; D004249:DNA Damage; D004260:DNA Repair; D016195:G2 Phase; D019398:Genes, BRCA1; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008938:Mitosis; D017239:Paclitaxel / Q000494:pharmacology; D013312:Stress, Physiological; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
D019313:BRCA1 Protein; D016159:Tumor Suppressor Protein p53; D007371:Interferon-gamma; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D017239:Paclitaxel