Mitochondrial inhibition of uracil-DNA glycosylase is not mutagenic.
BACKGROUND
Uracil 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.


RESULTS
In 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.


CONCLUSIONS
These 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.
Kachhap
Sushant
S
Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Bunting-Blaustein Cancer Research Building, 1650 Orleans St., Baltimore, MD 21231, USA. sushantkk@yahoo.com <sushantkk@yahoo.com>
Singh
Keshav K
KK
D001940:Breast / Q000166:cytology; D002460:Cell Line; D049109:Cell Proliferation; D045647:DNA Glycosylases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D014162:Transfection; D014498:Uracil / Q000378:metabolism; D051981:Uracil-DNA Glycosidase; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics
D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D014764:Viral Proteins; C027619:uracil-DNA glycosylase inhibitor protein, B. subtilis bacteriophage; D014498:Uracil; D011451:Prostaglandin-Endoperoxide Synthases; D045647:DNA Glycosylases; D051981:Uracil-DNA Glycosidase