Breast cancer gene 1 (BRCA1): Role in cell cycle regulation and DNA repair—perhaps through transcription

Abstract

Mutations of BRCA1 gene are associated with more than half the cases of hereditary breast cancer. Breast cancer formation in BRCA1 mutation carriers is generally accompanied by loss of the wild-type allele, suggesting that BRCA1 protein may function as a tumor suppressor. The human BRCA1 gene encodes a nuclear protein of 1863 amino acids. Although several lines of evidences suggest that BRCA1 protein may have a role to play in cell cycle regulation, DNA repair, and other processes, the exact mechanism of functioning by BRCA1 protein is not clear. Recent evidences from several laboratories suggest that BRCA1 may regulate the expression of many genes like p21(WAF1/CIP1), Gadd45, Cyclin B1, DBB2, XPC, 14-3-3ó and others at the level of transcription. These BRCA1-regulated gene products have been implicated directly or indirectly in cell cycle regulation and DNA repair. Thus a plausible model is proposed in which BRCA1 protein may bring its effects on cell cycle and DNA repair through its ability to modulate gene expression at the level of transcription.

Estrogen receptor corepressors -- a role in human breast cancer?

“…How does this translate to the biology of breast cancer cells? Not surprisingly, several ERα corepressors (such as SAFB1 and BRCA1) are able to block cell cycle progression (Townson et al 2000, Venkitaraman 2002, Somasundaram 2003. Also, SAFB1 overexpression significantly inhibits both anchorage-dependent and -independent growth of breast cancer cell lines (Townson et al 2000 and Oesterreich et al, unpublished results).…”

Dna Extraction and PCR Diagnosis of Breast Cancer Patients Among the Population of Tripura.

“…But it is considered that mutation in the BRCA1 and BRCA2 genes profoundly increase the risk of developing breast and/or ovarian cancer among women. Although their mechanism of action is not yet fully elucidated it is assumed that these genes play a key role in important cellular pathways including response to DNA damage, transcription, and interaction with other proteins involved in DNA repair and apoptosis [15][16]. This study revealed that PCR amplification that was carried out by using specific 141 primers (BRCA1 and BRCA2) are shown positive in case of breast cancer and shown negative in control sample (Fig-2).…”

Adverse Effect of Mobile Phone on Tp53, Brcai Genes and Dna Fragmentation in Albino Rat Liver

“…On the other hand, Hung, et al [34] reported that EMR exposure did not produce significant changes in cell numbers, cell cycle distribution, or level of DNA damage or global gene expression. The mutation in BRCAI gene leads to multiple genetic alterations including the inactivation of TP53 gene and activation of a number of oncogenes as reported by Somasundaram [35]. Whereas mutations in TP53 seem to occur at a very high frequency in BRCAI mutation, suggesting that P53 might be an important checkpoint for BRCAI associated tumorigenesis [36].…”