Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nuclear gene MIP1 is strictly required for mitochondrial DNA replication and mitochondrial DNA polymerase activity (Genga, A., Bianchi, L., and Foury, F. (1986) J. Biol. Chem. 261, 9328-9332). The MIP1 gene was cloned by genetic complementation of the mip1-1 allele after cell transformation with a yeast genomic library and was mapped to the right arm of chromosome XV about 20 centimorgans distal to the cpa1 gene by Southern blot hybridization and tetrad analysis. The mapping of the 5' ends of the MIP1 transcript and the nucleotide sequence analysis of a 4.7-kilobase DNA fragment complementing the mip1-1 allele allowed the determination of an open reading frame of 3762 nucleotides encoding a basic protein of 143.5 kDa. The following data show that the MIP1 gene encodes the catalytic subunit of the replicative mitochondrial DNA polymerase. 1) The mutant ts71 exhibits both a thermosensitive mitochondrial DNA replication in vivo and a thermosensitive mitochondrial DNA polymerase activity is observed, when compared to that of the wild type strain. 3) Chromosomal disruption of the MIP1 gene by an 80% deletion of the gene and its replacement by URA3 gene is not lethal to the cell but elicits total loss of mitochondrial DNA and mitochondrial DNA polymerase activity. 4) The MIP1 protein exhibits sequence similarities with both eukaryotic nuclear DNA polymerases and reverse transcriptases. There is no significant resemblance with prokaryotic DNA polymerases.
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PMID:Cloning and sequencing of the nuclear gene MIP1 encoding the catalytic subunit of the yeast mitochondrial DNA polymerase. 268 80

Our laboratory has reported that deoxyribonucleoside triphosphate (dNTP) pools in rat tissue mitochondria are highly asymmetric, with dGTP predominating, and that the imbalance probably contributes toward the high spontaneous mutation rate of the mitochondrial genome. Ferraro et al. (Ferraro, P., Nicolosi, L., Bernardi, P., Reichard, P., and Bianchi, V. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 18586-18591) have challenged these findings, based upon their studies of mouse liver mitochondria. Moreover, they have identified a potential artifact in the DNA polymerase-based assay for dNTPs, based upon overestimation of dGTP when GTP levels in extracts are much higher than dGTP levels. We measured ribonucleoside triphosphate (rNTP) pools in rat mitochondrial extracts and found that GTP pools exceed dGTP pools by 50-fold or less, not enough to interfere with the dGTP assay. Analysis of dNTP pools in state 3 mitochondria, after incubation with ADP and oxidizable substrates, gave similar results. We confirmed our earlier finding that rat mitochondrial dNTP pools are highly asymmetric. dNTP pools in cytosolic extracts are uniformly low, suggesting that the dNTP pool asymmetry arises within the mitochondrion. Moreover, we found rat tissue rNTP pools to be even more highly asymmetric, with ATP, for example, at least 2 orders of magnitude more abundant than CTP in liver extracts. This finding raises the possibility that transcription of the mitochondrial genome is more error-prone than transcription in the nucleus.
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PMID:Nucleoside triphosphate pool asymmetry in mammalian mitochondria. 2145 2