The cloning, genomic structure, localization, and expression of human deoxyribonuclease II beta

Acidic endonuclease activity is present in all cells in the body and much o f this can be attributed to the previously cloned and ubiquitously expresse d 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 thi s cDNA, which we term deoxyribonuclease II beta (DNase II beta) and compari son 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 e xhibits extensive homology to DNase II alpha including an amino-terminal si gnal peptide and a conserved active site, and has many of the regions of id entity that are conserved in homologs in other mammals as well as C. elegan s and Drosophila. The gene encoding DNase II beta has identical splice site s to DNase II alpha. Human DNase II beta is highly expressed in the salivar y gland, and at low levels in trachea, lung, prostate, lymph node, and test is, whereas DNase II alpha is ubiquitously expressed in all tissues. The ex pression pattern of human DNase II beta suggests that it may function prima rily 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 DN ase 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 betw een human and mouse DNase II beta. (C) 2001 Elsevier Science B.V. All right s reserved.