Maul G G, Jensen D E, Ishov A M, Herlyn M, Rauscher F J
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Cell Growth Differ. 1998 Sep;9(9):743-55.
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.
乳腺癌/卵巢癌易感基因产物BRCA1的功能及细胞内定位一直存在争议。为了清楚了解其定位以及与其他核结构的相对位置，我们制备了一种新的单克隆抗体，并通过免疫组织化学技术与其他BRCA1抗体进行了表征。每种抗体都能特异性检测到定位于特定核区域的BRCA1，且在多种细胞中均如此，并且呈细胞周期依赖性。然而，所有抗体也与中心体区域发生交叉反应，这表明BRCA1也定位于这个重要的有丝分裂成分。我们发现含BRCA1的核区域不同于任何明确界定的核区域。然而，我们发现参与异染色质维持的含染色质结构域蛋白HP1α与细胞周期相关的部分重叠。细胞刺激，如热休克和疱疹病毒感染，会使BRCA1从其区域分散。相反，腺病毒5感染会将BRCA1招募到病毒转录和复制区域。BRCA1的这些不同分布可能为其功能提供线索。
