REPAIR OF MITOCHONDRIAL-DNA AFTER VARIOUS TYPES OF DNA DAMAGE IN CHINESE-HAMSTER OVARY CELLS
REPAIR OF MITOCHONDRIAL-DNA AFTER VARIOUS TYPES OF DNA DAMAGE IN CHINESE-HAMSTER OVARY CELLS
复制标题
DOI：
10.1093/carcin/13.11.1967
复制
发表时间：
1992-11-01
期刊：
影响因子：
4.7
通讯作者：
BOHR, VA
中科院分区：
文献类型：
--
作者：
LEDOUX, SP;WILSON, GL;BOHR, VA
使用最近发展起来的评估基因特异性DNA修复的方法，我们已经证明，不仅可以研究线粒体DNA修复，而且可以直接比较同一生物样本中的线粒体和核DNA修复。复杂的酶机制识别和修复核DNA损伤，但长期以来一直认为线粒体中没有DNA修复。因此，为了更清楚地描述线粒体中有哪些DNA修复机制发挥作用，我们研究了线粒体DNA中几个特定DNA损伤的修复。它们包括环丁烷二聚体、顺铂链内加合物、顺铂链间交联物和碱不稳定部位。我们发现，线粒体DNA中的嘧啶二聚体和复杂的烷基化损伤不能修复，顺铂链内交联物的修复也很少。与之相反，顺铂的链间交联键有有效的修复，在24小时内约有70%的损伤被清除。此外，暴露于甲基亚硝脲后的N-甲基嘌呤也有有效的修复，约70%的损伤在24小时前被清除。这些研究结果表明，线粒体DNA损伤的修复能力取决于损伤剂产生的损伤类型。我们推测，线粒体DNA存在类似于核DNA碱基切除机制的过程，但没有核苷酸切除修复机制来移除这个细胞器中更大的病变。
Using methodology recently developed to assess gene-specific DNA repair, we have demonstrated that it is possible not only to study mitochondrial DNA repair, but also directly to compare mitochondrial and nuclear DNA repair in the same biological sample. Complex enzymatic mechanisms recognize and repair nuclear DNA damage, but it has long been thought that there was no DNA repair in mitochondria. Therefore, in an attempt to delineate more clearly which DNA repair mechanisms, if any, are functioning in mitochondria, we have investigated the repair of several specific DNA lesions in mitochondrial DNA. They include cyclobutane dimers, cisplatin intrastrand adducts, cisplatin interstrand crosslinks and alkali-labile sites. We find that pyrimidine dimers and complex alkylation damage are not repaired in mitochondrial DNA, and that there is minimal repair of cisplatin intrastrand crosslinks. In contrast, there is efficient repair of cisplatin interstrand crosslinks as evidenced by approximately 70% of the lesions being removed by 24 h. Additionally, there is efficient repair of N-methylpurines following exposure to methylnitrosourea with approximately 70% of the lesions being removed by 24 h. The results of these studies reveal that repair capacity of mitochondrial DNA damage depends upon the type of lesion produced by the damaging agent. We speculate that a process similar to the base excision mechanism for nuclear DNA exists for mitochondrial DNA but that there is no nucleotide excision repair mechanism to remove more bulky lesions in this organelle.