Medicinal Plant Resources and Protection Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
Department of Cancer Genetics and Epigenetics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
J Mol Cell Biol. 2024 Oct 21;16(5). doi: 10.1093/jmcb/mjae019.
Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes. They widely vary in substrates, causing differentiation in cleavage patterns and having a diversified role in maintaining genetic material. Through cellular evolution of prokaryotic to eukaryotic, nucleases become structure-specific in recognizing its own or foreign genomic DNA/RNA configurations as its substrates, including flaps, bubbles, and Holliday junctions. These special structural configurations are commonly found as intermediates in processes like DNA replication, repair, and recombination. The structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer cells. In this article, we review their roles in various pathways, including Okazaki fragment maturation during DNA replication, end resection in homology-directed recombination repair of DNA double-strand breaks, DNA excision repair and apoptosis DNA fragmentation in response to exogenous DNA damage, and HIV life cycle. As the nucleases serve as key points for the DNA dynamics, cellular apoptosis, and cancer cell survival pathways, we discuss the efforts in the field in developing the therapeutic regimens, taking advantage of recently available knowledge of their diversified structures and functions.
核酸酶是一类能够水解基因组中磷酸二酯键的酶超家族。它们在底物上广泛变化，导致切割模式的分化，并在维持遗传物质方面具有多样化的作用。通过原核到真核的细胞进化，核酸酶在识别自身或外来基因组 DNA/RNA 构象作为其底物时变得具有结构特异性，包括发夹、气泡和 Holliday 连接。这些特殊的结构构象通常作为 DNA 复制、修复和重组等过程中的中间体出现。结构特异性和多样化的功能使它们成为维持正常和癌细胞中基因组完整性和进化的必要条件。在本文中，我们回顾了它们在各种途径中的作用，包括 DNA 复制过程中 Okazaki 片段成熟、DNA 双链断裂同源定向重组修复中的末端切除、对外源 DNA 损伤的 DNA 切除修复和细胞凋亡 DNA 片段化以及 HIV 生命周期。由于核酸酶作为 DNA 动力学、细胞凋亡和癌细胞存活途径的关键点，我们讨论了在该领域的努力，利用最近获得的关于它们多样化结构和功能的知识，开发治疗方案。
