Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice

被引：275

作者：

Cerritelli, SM

Frolova, EG

Feng, CG

Grinberg, A

Love, PE

Crouch, RJ ^{[1
]}

机构：

[1] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA

[2] NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA

来源：

MOLECULAR CELL | 2003年 / 11卷 / 03期

关键词：

D O I：

10.1016/S1097-2765(03)00088-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：807 / 815

页数：9

共 49 条

[1] The absence of ribonuclease H1 or H2 alters the sensitivity of Saccharomyces cerevisiae to hydroxyurea, caffeine and ethyl methanesulphonate:: implications for roles of RNases H in DNA replication and repair [J].