DNase II: genes, enzymes and function

Abstract

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.