Evans Cory J, Aguilera Renato J
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
Gene. 2003 Dec 11;322:1-15. doi: 10.1016/j.gene.2003.08.022.
Deoxyribonuclease (DNase) II, which was discovered more than 50 years ago, is a mammalian endonuclease that functions optimally at acid pH in the absence of divalent cations. Its lysosomal localization and ubiquitous tissue distribution suggested that this enzyme played a role in the degradation of exogenous DNA encountered by phagocytosis, although the relative importance of such a role was unknown. Subsequent investigations also suggested that DNase II was important for DNA fragmentation and degradation during cell death. Within the last few years, our work and that of others has lead to the cloning of various mammalian DNase II genes as well as the identification and characterization of highly homologous genes in the invertebrates Caenorhabditis elegans and Drosophila melanogaster. Interestingly, studies of the C. elegans DNase II homolog NUC-1 were the first to suggest that DNase II enzymes were fundamentally important in engulfment-mediated DNA degradation, particularly that associated with programmed cell death, due to the presence of persistent apoptotic-cell nuclei within phagocytic cells in nuc-1 mutants. Similarly, mutation of the Drosophila DNase II-like gene was found to result in the accumulation of low-molecular-weight DNA throughout the animals. Homozygous mutation (knockout) of the DNase II gene in mice revealed a much more complex and extensive phenotype including perinatal lethality. The lethality of DNase II-knockout mice is likely the result of multiple developmental defects, the most obvious being a loss of definitive erythropoiesis. Closer examination revealed that a defect in engulfment-mediated DNA degradation is the primary defect in DNase II-null mice. In this review, we have compiled information from studies on DNase II from various organisms to provide a consensus model for the role of DNase II enzymes in DNA degradation.
脱氧核糖核酸酶（DNase）II于50多年前被发现，是一种哺乳动物内切核酸酶，在没有二价阳离子的情况下，在酸性pH值下发挥最佳功能。其溶酶体定位和广泛的组织分布表明，这种酶在吞噬作用中遇到的外源DNA降解中发挥作用，尽管这种作用的相对重要性尚不清楚。随后的研究还表明，DNase II在细胞死亡期间的DNA片段化和降解中很重要。在过去几年中，我们和其他人的工作导致了各种哺乳动物DNase II基因的克隆，以及在无脊椎动物秀丽隐杆线虫和黑腹果蝇中鉴定和表征高度同源的基因。有趣的是，对秀丽隐杆线虫DNase II同源物NUC-1的研究首次表明，DNase II酶在吞噬介导的DNA降解中至关重要，特别是与程序性细胞死亡相关的降解，因为在nuc-1突变体的吞噬细胞中存在持续的凋亡细胞核。同样，发现果蝇DNase II样基因的突变导致整个动物体内低分子量DNA的积累。小鼠中DNase II基因的纯合突变（敲除）揭示了一个更加复杂和广泛的表型，包括围产期致死率。DNase II敲除小鼠的致死率可能是多种发育缺陷的结果，最明显的是确定性红细胞生成的丧失。进一步检查发现，吞噬介导的DNA降解缺陷是DNase II基因缺失小鼠的主要缺陷。在这篇综述中，我们汇编了来自各种生物体中DNase II研究的信息，以提供一个关于DNase II酶在DNA降解中作用的共识模型。
