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果蝇中的双重凋亡 DNA 片段化系统:Drep2 是一种新型核酸内切酶,其活性受 Drep3 抑制。

Dual apoptotic DNA fragmentation system in the fly: Drep2 is a novel nuclease of which activity is inhibited by Drep3.

机构信息

School of Biotechnology and Graduate School of Biochemistry, Yeungnam University, Gyeongsan, Republic of Korea.

出版信息

FEBS Lett. 2012 Sep 21;586(19):3085-9. doi: 10.1016/j.febslet.2012.07.056. Epub 2012 Jul 28.

DOI:10.1016/j.febslet.2012.07.056
PMID:22850116
Abstract

DNA fragmentation is the hallmark of apoptotic cells and mainly mediated by the DNA fragmentation factor DFF40(CAD)/DFF45(ICAD). DFF40 is a novel nuclease, whereas DFF45 is an inhibitor that can suppress the nuclease activity. Apoptotic DNA fragmentation in the fly is controlled by four DFF-related proteins, known as Drep1, 2, 3 and 4. However, the functions of Drep2 and Drep3 are totally unknown. Here, we found that Drep2 is a novel nuclease whose activity is inhibited by Drep3 through a tight interaction with the CIDE domain. Our results suggest that the fly has dual apoptotic DNA fragmentation systems: Drep1: Drep4 and Drep2: Drep3 complexes.

摘要

DNA 碎片化是细胞凋亡的标志,主要由 DNA 碎片化因子 DFF40(CAD)/DFF45(ICAD)介导。DFF40 是一种新型核酸酶,而 DFF45 是一种抑制剂,可以抑制核酸酶活性。在果蝇中,凋亡性 DNA 碎片化受四种 DFF 相关蛋白(称为 Drep1、2、3 和 4)控制。然而,Drep2 和 Drep3 的功能完全未知。在这里,我们发现 Drep2 是一种新型核酸酶,其活性受到 Drep3 的抑制,通过与 CIDE 结构域的紧密相互作用。我们的结果表明,果蝇具有双重凋亡性 DNA 碎片化系统:Drep1:Drep4 和 Drep2:Drep3 复合物。

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Crystal structure and mutation analysis revealed that DREP2 CIDE forms a filament-like structure with features differing from those of DREP4 CIDE.晶体结构和突变分析表明,DREP2 CIDE 形成了一种类似纤维的结构,其特征与 DREP4 CIDE 不同。
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