The cloning, genomic structure, localization, and expression of human deoxyribonuclease IIβ

Acidic endonuclease activity is present in all cells in the body and much of this can be attributed to the previously cloned and ubiquitously expressed deoxyribonuclease II (DNase II). Database analysis revealed the existence of expressed sequence tags and genomic segments coding for a protein with considerable homology to DNase II. This report describes the cloning of this cDNA, which we term deoxyribonuclease II beta (DNase II beta) and comparison of its expression to that of the originally cloned DNase II (now termed DNase II alpha). The cDNA encodes a 357 amino acid protein. This protein exhibits extensive homology to DNase II alpha including an amino-terminal signal peptide and a conserved active site, and has many of the regions of identity that are conserved in homologs in other mammals as well as C. elegans and Drosophila. The gene encoding DNase II beta has identical splice sites to DNase II alpha. Human DNase II beta is highly expressed in the salivary gland, and at low levels in trachea, lung, prostate, lymph node, and testis, whereas DNase II alpha is ubiquitously expressed in all tissues. The expression pattern of human DNase II beta suggests that it may function primarily as a secreted enzyme. Human saliva was found to contain DNase II alpha, but after immunodepletion, considerable acid-active endonuclease remained which we presume is DNase II beta. We have localized the gene for human DNase II beta to chromosome 1p22.3 adjacent land in opposing orientation) to the human uricase pseudogene. Interestingly, murine DNase II beta is highly expressed in the liver. Uricase is also highly expressed in mouse but not human liver and this may explain the difference in expression patterns between human and mouse DNase II beta. (C) 2001 Elsevier Science B.V. All rights reserved.