DNA聚合酶在维持基因组稳定性中的多重功能及其相关疾病

The critical roles of DNA polymerases in genome stability and related human diseases

遗传物质的稳定传递是生命繁衍的根本。基因组DNA的精确复制和分配是遗传物质传递的基础,也是细胞周期两大最核心的生物学事件。DNA聚合酶作为催化合成DNA双链的酶,是复制过程中最重要的因子之一。尽管对这类酶的研究已有将近60年的历史,但依然是生命科学基础研究的前沿之一。真核生物中已知的DNA聚合酶有十几种,它们不仅参与正常基因组DNA合成过程,也参与DNA损伤情况下多种修复过程。如此众多的具有不同特性的DNA聚合酶在细胞内是如何分工与合作的,在正常细胞传代与环境胁迫等情况下维护基因组稳定性中的关键作用及其分子机制又是什么。更有意思的是,最近的肿瘤细胞比较基因组数据表明,多种DNA聚合酶基因突变与某些肿瘤和遗传疾病相关,从而为这些疾病致病机理研究与诊治提供了新的思路和方法。对上述DNA聚合酶相关核心问题的最新研究进展进行了综述。

Genome replication and segregation are two key processes during the cell cycle, which ensure the fidelity of transmission of genetic materials during cell proliferation. As the only enzyme responsible for synthesis of double helical DNA strand, DNA-dependent DNA polymerase is among the most important factors in DNA replication. In each eukaryotic cell, there are dozens of DNA polymerases with different characteristics, required for DNA replication and/or DNA repair. How do so many DNA pols divide their labor of DNA synthesis and coordinate each other？ What’s the underlying mechanism of different DNA pols in maintenance of genome stability under normal or stressed environment？ Furthermore, many somatic mutations in DNA pols have been identified to be associated with some particular tumors and genetic disorders. What’s the exact molecular etiology of these DNA polymeraserelated diseases？ These key issues of DNA polymerase are summarized in this review.