Molecular mechanisms and function of apoptosis Faculty of Pharmaceutical Science

细胞凋亡是从多细胞生物的细胞群落中清除不需要的细胞的机制。细胞凋亡调控异常可能在肿瘤、自身免疫性疾病、艾滋病、神经退行性疾病和畸形等疾病的发病机制中起一定作用。细胞凋亡的标志之一是基因组DNA酶促裂解成核小体寡聚体。鉴定负责细胞凋亡的核酸内切酶可能有助于解释这种细胞凋亡是如何调节的，以及为什么DNA被切割。在此，我们发现γ型DNA酶保留在胸腺细胞核中。DNA酶γ（Mr= 33 kDa）的DNA切割模式（3 '-羟基（OH）/5'-磷酰基（P）末端）及其对Zn^<2+>的敏感性与辐射或糖皮质激素处理诱导的胸腺细胞凋亡中观察到的一致，表明这种核酸内切酶是胸腺细胞凋亡机制的核心成分。

Apoptosis is a mechanism for eliminating unwanted cells from the cell community of multicellular organisms. Abnormalities in the regulation of apoptosis may play a part in the aetiology of cancer, autoimmune diseases, AIDS,degenerative nerve diseases and malformation. On of the hallmarks of apoptosis is the enzymatic cleavage of genomic DNA into nucleosomal oligomers. The identification of an endonuclease responsible for apoptosis might help to explain how this cell suiside is regulated and why DNA is cleaved. Here, we found that gamma type of DNase was retained in apoptptic rat thymocyte nuclei. The mode of DNA cleavage, 3'-hydroxyl (OH) /5'-phosphoryl (P) ends, by homogeneously purified DNase gamma (Mr=33kDa) and its Zn^<2+> sensitivity match those observed in apoptosis in thymocytes induced by irradiation or glucocorticoid treatment, indicating that this endonuclease is a central component of the thymic apoptosis machinery.