DNase γ, DNase I and caspase-activated DNase cooperate to degrade dead cells.

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. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Citation

Ryo Koyama, Tomoya Arai, Marie Kijima, Shoko Sato, Shigetoshi Miura, Makoto Yuasa, Daisuke Kitamura, Ryushin Mizuta. DNase γ, DNase I and caspase-activated DNase cooperate to degrade dead cells. Genes to cells : devoted to molecular & cellular mechanisms. 2016 Nov;21(11):1150-1163

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PMID: 27654959

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