Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice
Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice
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DOI：
10.1016/s1097-2765(03)00088-1
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发表时间：
2003-03-01
期刊：
影响因子：
16
通讯作者：
Crouch, RJ
中科院分区：
文献类型：
--
作者：
Cerritelli, SM;Frolova, EG;Crouch, RJ
虽然核糖核酸酶H （rnase H）长期以来一直与DNA代谢有关，但它们不是原核生物或单细胞真核生物生存所必需的。我们培育了Rnaseh1（-/-）小鼠来研究RNase H1在哺乳动物中的作用，并在零胚胎中观察到E8.5时发育停止。主要是细胞核的RNase H1的一部分靶向线粒体，在胚胎中缺乏它导致线粒体DNA含量显著降低，导致细胞凋亡。该报告将RNase H1与线粒体DNA的产生联系起来，为线粒体DNA复制的链偶联机制提供了直接支持。这些发现也对线粒体功能障碍的治疗和针对HIV结构相关的RNase H的药物开发具有重要意义。
Although ribonucleases H (RNases H) have long been implicated in DNA metabolism, they are not required for viability in prokaryotes or unicellular eukaryotes. We generated Rnaseh1(-/-) mice to investigate the role of RNase H1 in mammals and observed developmental arrest at E8.5 in null embryos. A fraction of the mainly nuclear RNase H1 was targeted to mitochondria, and its absence in embryos resulted in a significant decrease in mitochondrial DNA content, leading to apoptotic cell death. This report links RNase H1 to generation of mitochondrial DNA, providing direct support for the strand-coupled mechanism of mitochondrial DNA replication. These findings also have important implications for therapy of mitochondrial dysfunctions and drug development for the structurally related RNase H of HIV.