Hernandez Frank J
Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
Department of Bioengineering and Biosciences, TECNUN, Navarra University, Donostia, Spain.
Immunology. 2025 Mar;174(3):279-286. doi: 10.1111/imm.13884. Epub 2024 Dec 16.
The story of nucleases begins on the ancient battlefields of early Earth, where simple bacteria fought to survive against viral invaders. Nucleases are enzymes that degrade nucleic acids, with restriction endonucleases emerging as some of the earliest defenders, cutting foreign DNA to protect their bacteria hosts. However, bacteria sought more than just defence. They evolved the CRISPR-Cas system, an adaptive immune mechanism capable of remembering past invaders. The now-famous Cas9 nuclease, a key player in this system, has been harnessed for genome editing, revolutionising biotechnology. Over time, nucleases evolved from basic viral defence tools into complex regulators of immune function in higher organisms. In humans, DNases and RNases maintain immune balance by clearing cellular debris, preventing autoimmunity, and defending against pathogens. These enzymes have transformed from simple bacterial defenders to critical players in both human immunity and biotechnology. This review explores the evolutionary history of nucleases and their vital roles as protectors in the story of life's defence mechanisms.
核酸酶的故事始于早期地球的古老战场,当时简单的细菌为抵御病毒入侵者而奋力求生。核酸酶是一类能够降解核酸的酶,其中限制性内切核酸酶是最早出现的一些防御者,它们切割外来DNA以保护其细菌宿主。然而,细菌寻求的不仅仅是防御。它们进化出了CRISPR-Cas系统,这是一种能够记住过去入侵者的适应性免疫机制。如今著名的Cas9核酸酶是该系统的关键组成部分,已被用于基因组编辑,给生物技术带来了革命性的变化。随着时间的推移,核酸酶从基本的病毒防御工具演变成了高等生物免疫功能的复杂调节因子。在人类中,脱氧核糖核酸酶和核糖核酸酶通过清除细胞碎片、预防自身免疫和抵御病原体来维持免疫平衡。这些酶已从简单的细菌防御者转变为人类免疫和生物技术中的关键角色。本综述探讨了核酸酶的进化历史及其在生命防御机制故事中作为保护者的重要作用。