Localization of mitochondrial DNA base excision repair to an inner membrane-associated particulate fraction.
Localization of mitochondrial DNA base excision repair to an inner membrane-associated particulate fraction.
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DOI：
10.1093/nar/gki683
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发表时间：
2005
影响因子：
14.9
通讯作者：
Bohr, VA
中科院分区：
文献类型：
--
作者：
Stuart, JA;Mayard, S;Hashiguchi, K;Souza-Pinto, NC;Bohr, VA
相对于核DNA，线粒体DNA（mtDNA）含有高水平的氧化损伤。线粒体中存在完整的功能性DNA碱基切除修复（BER）途径，以修复氧化DNA损伤。然而，人们对线粒体内这一途径的组织知之甚少。在这里，我们提供的证据表明，线粒体BER蛋白是不能自由溶解，但强烈相关的内膜含颗粒部分。尿嘧啶DNA糖基化酶、氧代鸟嘌呤DNA糖基化酶和DNA聚合酶γ活性均与该颗粒部分共沉淀，并且通过洗涤剂（0.1%或1.0%NP 40）处理未与其分离。这些活性的颗粒关联不是由于它们结合线粒体DNA，而线粒体DNA本身与内膜相关，因为它们也定位于缺乏线粒体DNA的143 B（TK−）ρ0细胞的线粒体颗粒部分。然而，所有的BER活动，至少部分地溶解从颗粒部分用150-300 mM NaCl处理，这表明静电相互作用参与的协会。BER蛋白的表观固定化的生物学意义进行了讨论。
Mitochondrial DNA (mtDNA) contains high levels of oxidative damage relative to nuclear DNA. A full, functional DNA base excision repair (BER) pathway is present in mitochondria, to repair oxidative DNA lesions. However, little is known about the organization of this pathway within mitochondria. Here, we provide evidence that the mitochondrial BER proteins are not freely soluble, but strongly associated with an inner membrane-containing particulate fraction. Uracil DNA glycosylase, oxoguanine DNA glycosylase and DNA polymerase γ activities all co-sedimented with this particulate fraction and were not dissociated from it by detergent (0.1% or 1.0% NP40) treatment. The particulate associations of these activities were not due to their binding mtDNA, which is itself associated with the inner membrane, as they also localized to the particulate fraction of mitochondria from 143B (TK−) ρ0 cells, which lack mtDNA. However, all of the BER activities were at least partially solubilized from the particulate fraction by treatment with 150–300 mM NaCl, suggesting that electrostatic interactions are involved in the association. The biological implications of the apparent immobilization of BER proteins are discussed.
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影响因子：
4.8
作者：
Liu, MQ;Spremulli, L
通讯作者：
Spremulli, L
影响因子：
14.9
作者：
Ohtsubo, T;Nishioka, K;Nakabeppu, Y
通讯作者：
Nakabeppu, Y
影响因子：
14.9
作者：
Davis, AF;Ropp, PA;Copeland, WC
通讯作者：
Copeland, WC
影响因子：
7
作者：
Bogenhagen, DF;Wang, YS;Kobayashi, R
通讯作者：
Kobayashi, R
DOI：
10.1385/1-59259-284-8:259
发表时间：
2002-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Naviaux, Robert K
通讯作者：
Naviaux, Robert K