Disease relevance of MIP1

• MIP1 DNA polymerase of S. cerevisiae: structural similarity with the E. coli DNA polymerase I-type enzymes [1].
• We report the sequence of a 4.5-kb cDNA clone isolated from a human melanoma library which bears high amino acid sequence identity to the yeast mitochondrial (mt) DNA polymerase (Mip1p) [2].

High impact information on MIP1

• To shed light on the pathogenic mechanisms leading to these phenotypes, we have introduced in MIP1, the yeast homologue of POLG, two mutations equivalent to the human Y955C and G268A mutations, which are associated with dominant and recessive PEO, respectively [3].
• To rapidly characterize the effects of these mutations, we have developed a versatile system that enables the consequences of homologous mutations, introduced in situ into the yeast mtDNA polymerase gene MIP1, to be evaluated in vivo in haploid and diploid cells [4].
• The human POLG gene encodes the catalytic subunit of mitochondrial DNA polymerase gamma (pol gamma) [3].
• A bichaperone (Hsp70-Hsp78) system restores mitochondrial DNA synthesis following thermal inactivation of Mip1p polymerase [5].
• Interestingly, the reactivation of endogenous Mip1p contributed more significantly to the restoration of mtDNA synthesis than did import of newly synthesized Mip1p from the cytosol [5].

Biological context of MIP1

• The nuclear gene MIP1 encodes the mitochondrial DNA polymerase responsible for replicating the mitochondrial genome in Saccharomyces cerevisiae [6].
• Cloning and sequencing of the nuclear gene MIP1 encoding the catalytic subunit of the yeast mitochondrial DNA polymerase [7].
• The nuclear gene MIP1 is strictly required for mitochondrial DNA replication and mitochondrial DNA polymerase activity (Genga, A., Bianchi, L., and Foury, F [7].
• 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 [7].
• 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 [7].

Anatomical context of MIP1

• Absence of accessory subunit in the DNA polymerase gamma purified from yeast mitochondria [8].
• To confirm the identity of the final X.laevis clone, two antisera raised against peptide sequences were shown to react with DNA polymerase gamma purified from X.laevis oocyte mitochondria [9].
• In eukaryotic cells, there is much evidence to indicate that the replication of the mitochondrial genome is carried out by a specific DNA polymerase named DNA polymerase gamma [10].

Associations of MIP1 with chemical compounds

• Motif searches reveal a leucine zipper domain within a conserved N-terminal region of MIP1 [11].

Other interactions of MIP1

• The tightly linked VMA4 and MIP1 (encoding the mitochondrial DNA polymerase) genes are divergently transcribed from face-to-face promoters [12].
• Overexpression of the RNR1 gene rescues Saccharomyces cerevisiae mutants in the mitochondrial DNA polymerase-encoding MIP1 gene [13].
• 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 [7].
• Deletion of the sed1 gene results in a reduction in the quantity of Mip1p and also affects the levels of a mitochondrially-expressed protein, Cox3p [6].

References