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Published online before print April 2, 2007 as doi: 10.1096/fj.06-7977rev.

Maintaining precursor pools for mitochondrial DNA replication

Christopher K. Mathews and Shiwei Song

E-mail contact: mathewsc@onid.orst.edu

Among the human diseases that result from abnormalities in mitochondrial genome stability or maintenance are several that result from mutations affecting enzymes of deoxyribonucleoside triphosphate (dNTP) metabolism. In addition, it is evident that the toxicity of antiviral nucleoside analogs is determined in part by the extent to which their intracellular conversion to dNTP analogs occurs within the mitochondrion. Finally, recent work from this laboratory has shown considerable variation among different mammalian tissues with respect to mitochondrial dNTP pool sizes and has suggested that natural asymmetries in mitochondrial dNTP concentrations may contribute to the high rates at which the mitochondrial genome undergoes mutation. These factors suggest that much more information is needed about maintenance and regulation of dNTP pools within mammalian mitochondria. This review summarizes our current understanding and suggests directions for future research.--Mathews, C. K., Song, S. Maintaining precursor pools for mitochondrial DNA replication.




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