Functional characterization of DNase X, a novel endonuclease expressed in muscle cells

Los, Marek JanDepartment of Immunology and Cell Biology, University of Münster, Münster, and German Cancer Research Center, Division of Molecular Genome Analysis, Heidelberg, Germany (författare)

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 Ca2+ and Mg2+ and inhibited by Zn2+ 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.

NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
apoptotic endonuclease
caspase-activated dnase
death
epithelial-cells
fragmentation
human deoxyribonuclease-ii
human xq28
molecular-cloning
protein
rat parotid-gland

Neubuser, D.Department of Immunology and Cell Biology, University of Münster, Münster, and German Cancer Research Center, Division of Molecular Genome Analysis, Heidelberg, Germany (författare)
Coy, J. F.German Cancer Research Center, Division of Molecular Genome Analysis, Heidelberg, Germany (författare)
Mozoluk, M.Department of Immunology and Cell Biology, University of Münster, Münster (författare)
Poustka, A.German Cancer Research Center, Division of Molecular Genome Analysis, Heidelberg, Germany (författare)
Schulze-Osthoff, KlausDepartment of Immunology and Cell Biology, University of Münster, Münster, Germany (författare)
Department of Immunology and Cell Biology, University of Münster, Münster, and German Cancer Research Center, Division of Molecular Genome Analysis, Heidelberg, GermanyGerman Cancer Research Center, Division of Molecular Genome Analysis, Heidelberg, Germany (creator_code:org_t)

Ingår i:Biochemistry: American Chemical Society (ACS)39:25, s. 7365-73730006-29601520-4995

Av författaren/redakt...: Los, Marek Jan; Neubuser, D.; Coy, J. F.; Mozoluk, M.; Poustka, A.; Schulze-Osthoff, ...

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