Transactivation of repair genes by BRCA1.
Recent studies have identified a link between the BRCA1 tumor suppressor and transcriptional regulation of a group of genes involved in nucleotide excision repair. There is some controversy regarding the precise mechanism of upregulation of XPE DDB2 or XPC by BRCA1, with some evidence suggesting that p53 is involved in their regulation. Some evidence suggests BRCA1 may stabilize p53 and direct regulation of DNA repair genes, although how BRCA1 stabilizes p53 remains unclear and whether BRCA1 can upregulate DNA repair genes in a p53-independent manner remains a possibility. A transcriptional component to the action of BRCA1 and involvement of XP genes brings up new and interesting questions about breast cancer development and therapy.
El-Deiry
Wafik S
WS
Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, 415 Curie Boulevard, CRB 437A, Philadelphia, PA 19104, USA. wafik@mail.med.upenn.edu
D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D014983:Xeroderma Pigmentosum / Q000235:genetics
D019313:BRCA1 Protein; D009363:Neoplasm Proteins; D011506:Proteins; D016159:Tumor Suppressor Protein p53