Nuclear redistribution of BRCA1 during viral infection.

The functions and the intracellular localization of the breast/ovarian susceptibility gene product, BRCA1, has been controversial. To arrive at a clear understanding of its localization and relative position to other nuclear structures, a new monoclonal antibody was produced and characterized by immunohistochemical techniques with other BRCA1 antibodies. Each of the antibodies specifically detected BRCA1 as localized to specific nuclear domains and did so in a variety of cells and in a cell cycle-dependent manner. However, all antibodies also cross-reacted with the centrosomal domain, suggesting that BRCA1 is also localized to this important mitotic component. We found that the BRCA1-containing nuclear domains are different than any of the well-defined nuclear domains. However, a cell cycle-related partial overlap was found for HP1alpha, a chromo-domain-containing protein involved in heterochromatin maintenance. Cellular stimuli, such as heat shock and herpes virus infection, dispersed BRCA1 from its domains. In contrast, infection with adenovirus 5 recruited BRCA1 to regions of viral transcription and replication. These disparate distributions of BRCA1 may provide clues to its function.