title: Functional characterization of DNase X, a novel endonuclease expressed in muscle cells.
abstract: The activation of endonucleases resulting in the degradation of genomic DNA is one of the most characteristic changes in apoptosis. Here, we report the characterization of a novel endonuclease, termed DNase X due to its X-chromosomal localization. The active nuclease is a 35 kDa protein with 39% identity to DNase I. When incubated with isolated nuclei, recombinant DNase X was capable of triggering DNA degradation at internucleosomal sites. Similarly to DNase I, the nuclease activity of DNase X was dependent on Ca(2+) and Mg(2+) and inhibited by Zn(2+) ions or chelators of bivalent cations. Overexpression of DNase X caused internucleosomal DNA degradation and induction of cell death associated with increased caspase activation. Despite the presence of two potential caspase cleavage sites, DNase X was processed neither in vitro nor in vivo by different caspases. Interestingly, after initiation of apoptosis DNase X was translocated from the cytoplasm to the nuclear compartment and aggregated as a detergent-insoluble complex. Abundant expression of DNase X mRNA was detected in heart and skeletal muscle cells, suggesting that DNase X may be involved in apoptotic or other biological events in muscle tissues.
authors.affiliation: Department of Immunology and Cell Biology, University of Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Los
authors.forename: D
authors.initials: D
authors.lastname: Neubüser
authors.forename: J F
authors.initials: JF
authors.lastname: Coy
authors.forename: M
authors.initials: M
authors.lastname: Mozoluk
authors.forename: A
authors.initials: A
authors.lastname: Poustka
authors.forename: K
authors.initials: K
authors.lastname: Schulze-Osthoff
mesh_terms: D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000201:enzymology; D003851:Deoxyribonucleases / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D011994:Recombinant Proteins; D003851:Deoxyribonucleases