BAP1 is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase with a wide array of biological activities. Studies in which advanced sequencing technologies were used have uncovered a link between BAP1 and human cancer. Somatic and germline mutations of the BAP1 gene have been identified in multiple human cancers, with a particularly high frequency in mesothelioma, uveal melanoma and clear cell renal cell carcinoma. BAP1 cancer syndrome highlights that all carriers of inherited BAP1-inactivating mutations develop at least one and often multiple cancers with high penetrance during their lifetime. These findings, together with substantial evidence indicating the involvement of BAP1 in many cancer-related biological activities, strongly suggest that BAP1 functions as a tumor suppressor. Nonetheless, the mechanisms that account for the tumor suppressor function of BAP1 have only begun to be elucidated. Recently, the roles of BAP1 in genome stability and apoptosis have drawn considerable attention, and they are compelling candidates for key mechanistic factors. In this review, we focus on genome stability and summarize the details of the cellular and molecular functions of BAP1 in DNA repair and replication, which are crucial for genome integrity, and discuss the implications for BAP1-associated cancer and relevant therapeutic strategies. We also highlight some unresolved issues and potential future research directions.

BAP1 是一种含有泛素 C 末端水解酶结构域的去泛素化酶，具有广泛的生物活性。使用先进测序技术的研究揭示了 BAP1 与人类癌症之间的联系。已在多种人类癌症中发现BAP1基因的体细胞和种系突变，在间皮瘤、葡萄膜黑色素瘤和透明细胞肾细胞癌中频率特别高。BAP1 癌症综合征强调所有遗传性BAP1的携带者- 失活突变在其一生中至少会发展出一种且通常是多种具有高外显率的癌症。这些发现连同大量证据表明 BAP1 参与许多与癌症相关的生物活动，强烈表明 BAP1 具有肿瘤抑制因子的功能。尽管如此，解释 BAP1 肿瘤抑制功能的机制才刚刚开始被阐明。最近，BAP1 在基因组稳定性和细胞凋亡中的作用引起了相当大的关注，并且它们是关键机制因子的引人注目的候选者。在这篇综述中，我们关注基因组稳定性并总结了 BAP1 在 DNA 修复和复制中的细胞和分子功能的细节，这对基因组完整性至关重要，并讨论对 BAP1 相关癌症和相关治疗策略的影响。我们还强调了一些未解决的问题和潜在的未来研究方向。