DNA polymerase β: A missing link of the base excision repair machinery in mammalian mitochondria.
DNA polymerase β: A missing link of the base excision repair machinery in mammalian mitochondria.
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DOI：
10.1016/j.dnarep.2017.10.011
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发表时间：
2017-12
期刊：
影响因子：
3.8
通讯作者：
Wilson SH
中科院分区：
文献类型：
--
作者：
Prasad R;Çağlayan M;Dai DP;Nadalutti CA;Zhao ML;Gassman NR;Janoshazi AK;Stefanick DF;Horton JK;Krasich R;Longley MJ;Copeland WC;Griffith JD;Wilson SH
线粒体基因组的完整性是哺乳动物细胞生存力的基础。由于线粒体DNA不断受到ATP产生过程中释放的氧自由基的攻击，DNA修复在去除线粒体DNA中氧化产生的损伤方面至关重要，但强碱基切除修复系统的存在尚未得到证实。在这里，我们解决了这样一个系统在哺乳动物线粒体中的存在，涉及主要的碱基损伤修复酶DNA聚合酶（pol）β。通过电镜-免疫金染色、免疫荧光共定位和生化实验，将Pol β定位于哺乳动物线粒体。纯化的线粒体提取物具有依赖于pol β的碱基切除修复活性。pol β缺陷小鼠成纤维细胞的线粒体DNA修复受损，并在过氧化氢处理后显示超氧自由基水平升高。电子显微镜下可见pol β缺陷成纤维细胞线粒体形态改变。这些结果表明，哺乳动物线粒体含有一个有效的碱基损伤修复系统，部分由pol β介导，因此pol β在维持线粒体基因组稳定性方面发挥作用。
Mitochondrial genome integrity is fundamental to mammalian cell viability. Since mitochondrial DNA is constantly under attack from oxygen radicals released during ATP production, DNA repair is vital in removing oxidatively generated lesions in mitochondrial DNA, but the presence of a strong base excision repair system has not been demonstrated. Here, we addressed the presence of such a system in mammalian mitochondria involving the primary base lesion repair enzyme DNA polymerase (pol) β. Pol β was localized to mammalian mitochondria by electron microscopic-immunogold staining, immunofluorescence co-localization and biochemical experiments. Extracts from purified mitochondria exhibited base excision repair activity that was dependent on pol β. Mitochondria from pol β-deficient mouse fibroblasts had compromised DNA repair and showed elevated levels of superoxide radicals after hydrogen peroxide treatment. Mitochondria in pol β-deficient fibroblasts displayed altered morphology by electron microscopy. These results indicate that mammalian mitochondria contain an efficient base lesion repair system mediated in part by pol β and thus pol β plays a role in preserving mitochondrial genome stability.
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影响因子：
2.9
作者：
Fortini, P;Pascucci, B;Dogliotti, E
通讯作者：
Dogliotti, E
影响因子：
14.9
作者：
Debéthune, L;Kohlhagen, G;Pommier, Y
通讯作者：
Pommier, Y
影响因子：
4.8
作者：
Choi, Jae H.;Williams, Jason;Shears, Stephen B.
通讯作者：
Shears, Stephen B.
DOI：
10.1385/1-59259-284-8:199
发表时间：
2002-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Bogenhagen, Daniel F
通讯作者：
Bogenhagen, Daniel F
影响因子：
6.1
作者：
Guo C;Sun L;Chen X;Zhang D
通讯作者：
Zhang D