Abstract
BackgroundUracil DNA glycosylase (UDG) plays a major role in repair of uracil formed due to deamination of cytosine. UDG in human cells is present in both the nucleus and mitochondrial compartments. Although, UDG's role in the nucleus is well established its role in mitochondria is less clear.ResultsIn order to identify UDG's role in the mitochondria we expressed UGI (uracil glycosylase inhibitor) a natural inhibitor of UDG in the mitochondria. Our studies suggest that inhibition of UDG by UGI in the mitochondria does not lead to either spontaneous or induced mutations in mtDNA. Our studies also suggest that UGI expression has no affect on cellular growth or cytochrome c-oxidase activity.ConclusionsThese results suggest that human cell mitochondria contain alternatives glycosylase (s) that may function as back up DNA repair protein (s) that repair uracil in the mitochondria.
Highlights
Mitochondrion plays an important role in various cellular functions ranging from synthesis of lipids to maintenance of ion homeostasis [1,2]
The mitochondrion has various active and passive safe guard strategies to deal with the damaging effects of reactive oxygen species (ROS) on the mitochondrial DNA, one of them being the repair of the lesions caused by the ROS production [3]
Generation of stable transfectants expressing uracil DNA glycosylase inhibitor (UGI) and Uracil DNA glycosylase (UDG) in the mitochondria Previous studies have shown that uracil DNA glycolyase can be inhibited by PBS2 phage protein UGI in a stoichiometric fashion [17,18]
Summary
Mitochondrion plays an important role in various cellular functions ranging from synthesis of lipids to maintenance of ion homeostasis [1,2]. The mitochondrion has various active and passive safe guard strategies to deal with the damaging effects of ROS on the mitochondrial DNA (mtDNA), one of them being the repair of the lesions caused by the ROS production [3]. Recent evidence indicates that DNA repair mechanism do function in the mitochondria [7,8,25,26]. Various enzymes that are involved in nuclear DNA repair have isoforms that are targeted to the mitochondria [9,10]. Whether these enzymes function in an identical fashion in the repair of both the nuclear and the mtDNA is not clear. UDG's role in the nucleus is well established its role in mitochondria is less clear
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