title: DNase γ, DNase I and caspase-activated DNase cooperate to degrade dead cells.
abstract: Serum endonucleases are essential for degrading the chromatin released from dead cells and preventing autoimmune diseases such as systemic lupus erythematosus. Serum DNase I is known as the major endonuclease, but recently, another endonuclease, DNase γ/DNase I-like 3, gained attention. However, the precise role of each endonuclease, especially that of DNase γ, remains unclear. In this study, we distinguished the activities of DNase γ from those of DNase I in mouse serum and concluded that both cooperated in degrading DNA during necrosis: DNase γ functions as the primary chromatolytic activity, causing internucleosomal DNA fragmentation, and DNase I as the secondary one, causing random DNA digestion for its complete degradation. These results were confirmed by two in vivo experimental mouse models, in which necrosis was induced, acetaminophen-induced hepatic injury and streptozotocin-induced β-cell necrosis models. We also determined that DNase γ functions as a backup endonuclease for caspase-activated DNase (CAD) in the secondary necrosis phase after γ-ray-induced apoptosis in vivo.
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba, 278-0022, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Koyama
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba, 278-0022, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Arai
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba, 278-0022, Japan.
authors.forename: Marie
authors.initials: M
authors.lastname: Kijima
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo, 125-8585, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo, 125-8585, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Miura
authors.affiliation: Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yuasa
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba, 278-0022, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitamura
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba, 278-0022, Japan.
authors.forename: Ryushin
authors.initials: R
authors.lastname: Mizuta
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D053836:DNA Degradation, Necrotic; D053938:DNA Fragmentation; D003851:Deoxyribonucleases / Q000097:blood*; D015253:Deoxyribonucleases, Type I Site-Specific / Q000097:blood*; D004706:Endodeoxyribonucleases / Q000097:blood*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes; D009336:Necrosis / Q000097:blood; D000075223:Poly-ADP-Ribose Binding Proteins; D013154:Spleen / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D000075223:Poly-ADP-Ribose Binding Proteins; C120774:aposome; D003851:Deoxyribonucleases; C499445:Dffb protein, mouse; D004706:Endodeoxyribonucleases; C000613995:casepase-activated DNase, mouse; C105124:deoxyribonuclease gamma; D015253:Deoxyribonucleases, Type I Site-Specific