自我造成的DNA链断裂与细胞死亡途径以及免疫和生殖细胞的基因多样性的建立有经典联系。此外，这种DNA损伤形式已成为肿瘤发展中致基因组不稳定的已知来源。然而，最近的研究表明，非致死性的DNA链断裂在包括分化和癌症治疗反应在内的多种细胞过程中发挥着不可或缺但被低估的作用。在机制上，这些生理性DNA断裂源自核酸酶的激活，最具代表性的是在凋亡性细胞死亡中诱导DNA断裂的特征。在本文中，我们概述了一个关键核酸酶，即半胱氨酸激活的DNase (CAD)的新兴生物学，以及如何定向激活或部署该酶可以导致不同的细胞命运结果。版权所有©2023 Elsevier Ltd.。保留所有权利。

Self-inflicted DNA strand breaks are canonically linked with cell death pathways and the establishment of genetic diversity in immune and germline cells. Moreover, this form of DNA damage is an established source of genome instability in cancer development. However, recent studies indicate that nonlethal self-inflicted DNA strand breaks play an indispensable but underappreciated role in a variety of cell processes, including differentiation and cancer therapy responses. Mechanistically, these physiological DNA breaks originate from the activation of nucleases, which are best characterized for inducing DNA fragmentation in apoptotic cell death. In this review, we outline the emerging biology of one critical nuclease, caspase-activated DNase (CAD), and how directed activation or deployment of this enzyme can lead to divergent cell fate outcomes.Copyright © 2023 Elsevier Ltd. All rights reserved.