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DNase γ, DNase I and caspase‐activated DNase cooperate to degrade dead cells
Author(s) -
Koyama Ryo,
Arai Tomoya,
Kijima Marie,
Sato Shoko,
Miura Shigetoshi,
Yuasa Makoto,
Kitamura Daisuke,
Mizuta Ryushin
Publication year - 2016
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12433
Subject(s) - endonuclease , dnase i hypersensitive site , biology , hypersensitive site , deoxyribonuclease i , microbiology and biotechnology , apoptotic dna fragmentation , necrosis , chromatin , apoptosis , dna fragmentation , dna , deoxyribonuclease , programmed cell death , biochemistry , genetics , base sequence
Serum endonucleases are essential for degrading the chromatin released from dead cells and preventing autoimmune diseases such as systemic lupus erythematosus. Serum DN ase I is known as the major endonuclease, but recently, another endonuclease, DN ase γ/ DN ase I‐like 3, gained attention. However, the precise role of each endonuclease, especially that of DN ase γ, remains unclear. In this study, we distinguished the activities of DN ase γ from those of DN ase I in mouse serum and concluded that both cooperated in degrading DNA during necrosis: DN ase γ functions as the primary chromatolytic activity, causing internucleosomal DNA fragmentation, and DN ase 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 DN ase γ functions as a backup endonuclease for caspase‐activated DN ase ( CAD ) in the secondary necrosis phase after γ‐ray‐induced apoptosis in vivo .