Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, University Mohammed V, Rabat, Morocco; Genomic Center of Human Pathologies, Faculty of medicine and Pharmacy, University Mohammed V, Rabat, Morocco.
Mol Genet Metab. 2021 May;133(1):35-48. doi: 10.1016/j.ymgme.2021.03.003. Epub 2021 Mar 10.
Autosomal hereditary recessive diseases characterized by genetic instability are often associated with cancer predisposition. Bloom syndrome (BS), a rare genetic disorder, with <300 cases reported worldwide, combines both. Indeed, patients with Bloom's syndrome are 150 to 300 times more likely to develop cancers than normal individuals. The wide spectrum of cancers developed by BS patients suggests that early initial events occur in BS cells which may also be involved in the initiation of carcinogenesis in the general population and these may be common to several cancers. BS is caused by mutations of both copies of the BLM gene, encoding the RecQ BLM helicase. This review discusses the different aspects of BS and the different cellular functions of BLM in genome surveillance and maintenance through its major roles during DNA replication, repair, and transcription. BLM's activities are essential for the stabilization of centromeric, telomeric and ribosomal DNA sequences, and the regulation of innate immunity. One of the key objectives of this work is to establish a link between BLM functions and the main clinical phenotypes observed in BS patients, as well as to shed new light on the correlation between the genetic instability and diseases such as immunodeficiency and cancer. The different potential implications of the BLM helicase in the tumorigenic process and the use of BLM as new potential target in the field of cancer treatment are also debated.
常染色体隐性遗传疾病，其特征为遗传不稳定性，往往与癌症易感性相关。布卢姆综合征（BS）是一种罕见的遗传疾病，全世界报告的病例<300 例，兼具这两种特征。实际上，BS 患者罹患癌症的风险比正常人高 150 至 300 倍。BS 患者罹患的癌症谱广泛，表明 BS 细胞中发生了早期初始事件，这些事件也可能参与了普通人群中癌症的发生，并且这些事件可能与多种癌症有关。BS 是由 BLM 基因的两个拷贝的突变引起的，该基因编码 RecQ BLM 解旋酶。本文综述了 BS 的不同方面，以及 BLM 在基因组监测和维护中的不同细胞功能，主要通过其在 DNA 复制、修复和转录过程中的主要作用。BLM 的活性对于着丝粒、端粒和核糖体 DNA 序列的稳定性以及固有免疫的调节至关重要。这项工作的一个关键目标是在 BLM 功能和 BS 患者观察到的主要临床表型之间建立联系，并阐明遗传不稳定性与免疫缺陷和癌症等疾病之间的相关性。还讨论了 BLM 解旋酶在肿瘤发生过程中的不同潜在影响，以及将 BLM 作为癌症治疗领域新的潜在靶标的用途。
