Localization of BRCA1 protein at the cellular level.

Based on its amino acid sequence and the existence of three nuclear localization signal (NLS)3 regions, BRCA1 is likely to be a cell cycle-dependent nuclear protein, regulated by cyclin-dependent kinases (cdk) and associated with nuclear proteins such as Rad51 and BARD1, involved in transcription regulation and participating in DNA replication checkpoints. However, many authors have also described a cytoplasmic expression pattern. Moreover, BRCA1 was present not only in a dot like pattern in the nucleus but also associated with a channel-like system of cytoplasm and endoplasmic reticulum invaginating into the nucleus. BRCA1 expression patterns can also be influenced by alternative splice variants and by cell cycle-dependent expression level and localization. Further ultrastructural and confocal studies using C-terminal antibodies, that do not react with C-terminal truncated form of BRCA1 should shed new light upon the exact localization of BRCA1.