Haitao Sun, Megan Luo, Mian Zhou, Li Zheng, Hongzhi Li, R Steven Esworthy, Binghui Shen
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引用次数: 0
摘要
核酸酶是水解基因组中磷酸二酯键的超级酶家族。它们的底物千差万别,导致裂解模式的差异,并在维持遗传物质方面发挥着多样化的作用。从原核细胞到真核细胞的细胞进化过程中,核酸酶具有结构特异性,能识别自身或外来基因组 DNA/RNA 构型作为底物,包括瓣膜、气泡和霍利迪连接。这些特殊的结构构型通常是 DNA 复制、修复和重组等过程的中间产物。结构的特异性和功能的多样性使它们对维持正常细胞和癌细胞基因组的完整性和进化至关重要。在本文中,我们将回顾它们在各种途径中的作用,包括 DNA 复制过程中的冈崎片段成熟、DNA 双链断裂同源定向重组修复中的末端切除、DNA 切除修复和外源性 DNA 损伤时的 DNA 片段凋亡以及 HIV 生命周期。由于核酸酶是 DNA 动态、细胞凋亡和癌细胞存活途径的关键点,我们将讨论该领域在开发治疗方案方面所做的努力,并利用最近获得的有关核酸酶多样化结构和功能的知识。
Structure-specific nucleases in genome dynamics and strategies for targeting cancers.
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 exogeneous 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.
期刊介绍:
The Journal of Molecular Cell Biology ( JMCB ) is a full open access, peer-reviewed online journal interested in inter-disciplinary studies at the cross-sections between molecular and cell biology as well as other disciplines of life sciences. The broad scope of JMCB reflects the merging of these life science disciplines such as stem cell research, signaling, genetics, epigenetics, genomics, development, immunology, cancer biology, molecular pathogenesis, neuroscience, and systems biology. The journal will publish primary research papers with findings of unusual significance and broad scientific interest. Review articles, letters and commentary on timely issues are also welcome.
JMCB features an outstanding Editorial Board, which will serve as scientific advisors to the journal and provide strategic guidance for the development of the journal. By selecting only the best papers for publication, JMCB will provide a first rate publishing forum for scientists all over the world.