Evidence for a role of FEN1 in maintaining mitochondrial DNA integrity
Evidence for a role of FEN1 in maintaining mitochondrial DNA integrity
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DOI：
10.1016/j.dnarep.2009.07.008
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发表时间：
2009-10-02
期刊：
影响因子：
3.8
通讯作者：
Sia, Elaine A.
中科院分区：
文献类型：
--
作者：
Kalifa, Lidza;Beutner, Gisela;Sia, Elaine A.
尽管负责基因组DNA复制和修复的核过程已被很好地表征，但涉及线粒体DNA（mtDNA）复制和修复的途径仍不清楚。DNA修复已被确定为在线粒体区室中特别重要，这是由于细胞器高度倾向于积累氧化DNA损伤。据推测，线粒体DNA损伤的持续积累和随后的突变可能在细胞衰老中起作用。线粒体碱基切除修复（mtBER）在对抗线粒体DNA氧化损伤中起着重要作用;然而，参与mtBER的蛋白质尚未完全表征。已经确定，在核长斑（LP）BEF期间，FEN 1负责DNA合成期间产生的5'瓣结构的切割。此外，已经在哺乳动物细胞系的线粒体提取物中观察到5'瓣的去除;然而，FEN 1的线粒体定位尚未被清楚地证明。在这项研究中，我们分析了删除酵母FEN 1同源物，RAD 27，在酿酒酵母mtDNA的稳定性的影响。我们的研究结果表明，Rad 27 p/FEN 1是本地化的酵母和小鼠的线粒体隔室，Rad 27 p在维持线粒体DNA的完整性具有重要的作用。(C)2009 Elsevier B. V.保留所有权利。
Although the nuclear processes responsible for genomic DNA replication and repair are well characterized, the pathways involved in mitochondrial DNA (mtDNA) replication and repair remain unclear. DNA repair has been identified as being particularly important within the mitochondrial compartment due to the organelle's high propensity to accumulate oxidative DNA damage. It has been postulated that continual accumulation of mtDNA damage and subsequent mutagenesis may function in cellular aging. Mitochondrial base excision repair (mtBER) plays a major role in combating mtDNA oxidative damage; however, the proteins involved in mtBER have yet to be fully characterized. It has been established that during nuclear long-patch (LP) BEF, FEN1 is responsible for cleavage of 5' flap structures generated during DNA synthesis. Furthermore, removal of 5' flaps has been observed in mitochondrial extracts of mammalian cell lines; yet, the mitochondrial localization of FEN1 has not been clearly demonstrated. In this study, we analyzed the effects of deleting the yeast FEN1 homolog, RAD27, on mtDNA stability in Saccharomyces cerevisiae. Our findings demonstrate that Rad27p/FEN1 is localized in the mitochondrial compartment of both yeast and mice and that Rad27p has a significant role in maintaining mtDNA integrity. (C) 2009 Elsevier B.V. All rights reserved.