Membrane association of mitochondrial DNA facilitates base excision repair in mammalian mitochondria
Membrane association of mitochondrial DNA facilitates base excision repair in mammalian mitochondria
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DOI：
10.1093/nar/gkp1143
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发表时间：
2010-03-01
影响因子：
14.9
通讯作者：
Lightowlers, Robert N.
中科院分区：
文献类型：
--
作者：
Boesch, Pierre;Ibrahim, Noha;Lightowlers, Robert N.
线粒体DNA编码一组13种多肽，并由于细胞器内ROS的产生而受到恒定的氧化应激。研究表明，线粒体中的DNA修复通过短补丁和长补丁碱基切除修复（BER）进行。在本文中，我们利用哺乳动物线粒体的天然能力来输入DNA，并研究修复系统在细胞器中的亚线粒体定位。结果表明，对应于mtDNA非编码区的序列与内膜以快速和饱和的方式相互作用。我们表明，含尿嘧啶的进口底物被纳入到peption和损伤驱动的DNA合成作为模板。进一步细分后，我们发现，修复合成补丁的长度不同的可溶性和颗粒部分。真正的长斑块BER合成发生在与颗粒部分相关的DNA上，而当含尿嘧啶的DNA进入可溶性部分时，发生切口驱动的DNA合成。我们的研究结果表明，协调BER所需的不同合作伙伴的相互作用，只发现在网站的DNA与膜。
Mitochondrial DNA encodes a set of 13 polypeptides and is subjected to constant oxidative stress due to ROS production within the organelle. It has been shown that DNA repair in the mitochondrion proceeds through both short- and long-patch base excision repair (BER). In the present article, we have used the natural competence of mammalian mitochondria to import DNA and study the sub-mitochondrial localization of the repair system in organello. Results demonstrate that sequences corresponding to the mtDNA non-coding region interact with the inner membrane in a rapid and saturable fashion. We show that uracil containing import substrates are taken into the mitochondrion and are used as templates for damage driven DNA synthesis. After further sub-fractionation, we show that the length of the repair synthesis patch differs in the soluble and the particulate fraction. Bona fide long patch BER synthesis occurs on the DNA associated with the particulate fraction, whereas a nick driven DNA synthesis occurs when the uracil containing DNA accesses the soluble fraction. Our results suggest that coordinate interactions of the different partners needed for BER is only found at sites where the DNA is associated with the membrane.