RESUMO

Human and yeast mitochondrial DNA polymerases (DNAPs), POLG and Mip1, are related by evolution to bacteriophage DNAPs. However, mitochondrial DNAPs contain unique amino and carboxyl-terminal extensions that physically interact. Here we describe that N-terminal deletions in Mip1 polymerases abolish polymerization and decrease exonucleolytic degradation, whereas moderate C-terminal deletions reduce polymerization. Similarly, to the N-terminal deletions, an extended C-terminal deletion of 298 amino acids is deficient in nucleotide addition and exonucleolytic degradation of double and single-stranded DNA. The latter observation suggests that the physical interaction between the amino and carboxyl-terminal regions of Mip1 may be related to the spread of pathogenic POLG mutant along its primary sequence.

Assuntos

DNA Polimerase I/metabolismo , DNA Fúngico/biossíntese , DNA Mitocondrial/biossíntese , Proteínas Mitocondriais/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Domínio Catalítico , DNA Polimerase I/genética , DNA Polimerase gama/genética , DNA Polimerase gama/metabolismo , DNA Fúngico/genética , DNA Mitocondrial/genética , Humanos , Proteínas Mitocondriais/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética