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哺乳动物线粒体 DNA 复制中间体本质上是双链的,但含有大量的 RNA/DNA 杂交区域。

Mammalian mitochondrial DNA replication intermediates are essentially duplex but contain extensive tracts of RNA/DNA hybrid.

机构信息

Department of Forensic Medicine and Tampere University Hospital, FI-33014 University of Tampere, Finland.

出版信息

J Mol Biol. 2010 Apr 16;397(5):1144-55. doi: 10.1016/j.jmb.2010.02.029. Epub 2010 Feb 23.

DOI:10.1016/j.jmb.2010.02.029
PMID:20184890
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2857715/
Abstract

We demonstrate, using transmission electron microscopy and immunopurification with an antibody specific for RNA/DNA hybrid, that intact mitochondrial DNA replication intermediates are essentially duplex throughout their length but contain extensive RNA tracts on one strand. However, the extent of preservation of RNA in such molecules is highly dependent on the preparative method used. These findings strongly support the strand-coupled model of mitochondrial DNA replication involving RNA incorporation throughout the lagging strand.

摘要

我们利用电镜和针对 RNA/DNA 杂交的抗体免疫纯化的方法证实,完整的线粒体 DNA 复制中间体在其全长上基本上都是双链的,但在一条链上含有广泛的 RNA 片段。然而,在这些分子中 RNA 的保存程度高度依赖于所使用的制备方法。这些发现强烈支持涉及整个滞后链 RNA 掺入的线粒体 DNA 复制的链偶联模型。

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本文引用的文献

1
Native R-loops persist throughout the mouse mitochondrial DNA genome.天然R环存在于整个小鼠线粒体DNA基因组中。
J Biol Chem. 2008 Dec 26;283(52):36743-51. doi: 10.1074/jbc.M806174200. Epub 2008 Nov 5.
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RNase H activity: structure, specificity, and function in reverse transcription.核糖核酸酶H活性:逆转录中的结构、特异性及功能
Virus Res. 2008 Jun;134(1-2):86-103. doi: 10.1016/j.virusres.2007.12.007. Epub 2008 Feb 7.
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Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes.线粒体DNA解旋酶Twinkle和聚合酶POLG的催化突变体的表达导致不同的复制停滞表型。
Nucleic Acids Res. 2007;35(10):3238-51. doi: 10.1093/nar/gkm215. Epub 2007 Apr 22.
4
Replication fork regression in repetitive DNAs.重复DNA中的复制叉回归
Nucleic Acids Res. 2006;34(20):6044-50. doi: 10.1093/nar/gkl757. Epub 2006 Oct 28.
5
Replication of vertebrate mitochondrial DNA entails transient ribonucleotide incorporation throughout the lagging strand.脊椎动物线粒体DNA的复制需要在整个滞后链中短暂掺入核糖核苷酸。
EMBO J. 2006 Nov 15;25(22):5358-71. doi: 10.1038/sj.emboj.7601392. Epub 2006 Oct 26.
6
Alterations to the expression level of mitochondrial transcription factor A, TFAM, modify the mode of mitochondrial DNA replication in cultured human cells.线粒体转录因子A(TFAM)表达水平的改变会改变培养的人类细胞中线粒体DNA的复制模式。
Nucleic Acids Res. 2006;34(20):5815-28. doi: 10.1093/nar/gkl703. Epub 2006 Oct 24.
7
Replication of mitochondrial DNA occurs by strand displacement with alternative light-strand origins, not via a strand-coupled mechanism.线粒体DNA的复制通过链置换和交替轻链起始点进行,而非通过链偶联机制。
Genes Dev. 2005 Oct 15;19(20):2466-76. doi: 10.1101/gad.1352105.
8
A bidirectional origin of replication maps to the major noncoding region of human mitochondrial DNA.一个双向复制起点定位于人类线粒体DNA的主要非编码区域。
Mol Cell. 2005 Jun 10;18(6):651-62. doi: 10.1016/j.molcel.2005.05.002.
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Bidirectional replication initiates at sites throughout the mitochondrial genome of birds.双向复制起始于鸟类线粒体基因组的各个位点。
J Biol Chem. 2005 Feb 4;280(5):3242-50. doi: 10.1074/jbc.M411916200. Epub 2004 Nov 20.
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Mammalian mitochondrial DNA replicates bidirectionally from an initiation zone.哺乳动物线粒体DNA从一个起始区域双向复制。
J Biol Chem. 2003 Dec 19;278(51):50961-9. doi: 10.1074/jbc.M308028200. Epub 2003 Sep 23.