The breast cancer type 1 susceptibility protein (BRCA1) and its partner – the BRCA1-associated RING domain protein 1 (BARD1) – are key players in a plethora of fundamental biological functions including, among others, DNA repair, replication fork protection, cell cycle progression, telomere maintenance, chromatin remodeling, apoptosis and tumor suppression. However, mutations in their encoding genes transform them into dangerous threats, and substantially increase the risk of developing cancer and other malignancies during the lifetime of the affected individuals. Understanding how BRCA1 and BARD1 perform their biological activities therefore not only provides a powerful mean to prevent such fatal occurrences but can also pave the way to the development of new targeted therapeutics. Thus, through this review work we aim at presenting the major efforts focused on the functional characterization and structural insights of BRCA1 and BARD1, per se and in combination with all their principal mediators and regulators, and on the multifaceted roles these proteins play in the maintenance of human genome integrity.

乳腺癌 1 型易感蛋白 (BRCA1) 及其伙伴 - BRCA1 相关环结构域蛋白 1 (BARD1) - 是众多基本生物学功能的关键参与者，其中包括 DNA 修复、复制叉保护、细胞周期进展、端粒维持、染色质重塑、细胞凋亡和肿瘤抑制。然而，它们编码基因的突变将它们变成了危险的威胁，并大大增加了受影响个体在一生中患癌症和其他恶性肿瘤的风险。因此，了解 BRCA1 和 BARD1 如何发挥其生物活性不仅为预防此类致命事件提供了强有力的手段，而且还可以为开发新的靶向疗法铺平道路。因此，本身并与它们所有的主要介质和调节剂相结合，以及这些蛋白质在维持人类基因组完整性中所起的多方面作用。