Amino and carboxy-terminal extensions of yeast mitochondrial DNA polymerase assemble both the polymerization and exonuclease active sites

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 p...

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Bibliographic Details
Published in:Mitochondrion 2019-11, Vol.49, p.166-177
Main Authors: Trasviña-Arenas, Carlos H., Hoyos-Gonzalez, Nallely, Castro-Lara, Atzimba Y., Rodriguez-Hernandez, Annia, Sanchez-Sandoval, María E., Jimenez-Sandoval, Pedro, Ayala-García, Víctor M., Díaz-Quezada, Corina, Lodi, Tiziana, Baruffini, Enrico, Brieba, Luis G.
Format: Article
Language:English
Subjects:
Catalytic Domain
DNA polymerase
DNA Polymerase gamma - genetics
DNA Polymerase gamma - metabolism
DNA Polymerase I - genetics
DNA Polymerase I - metabolism
DNA replication
DNA, Fungal - biosynthesis
DNA, Fungal - genetics
DNA, Mitochondrial - biosynthesis
DNA, Mitochondrial - genetics
Enzyme kinetics
Humans
Medical Biotechnology
Medicinsk bioteknologi
Mitochondria
Mitochondrial Proteins - genetics
Mitochondrial Proteins - metabolism
Regulation
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Structure-function
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Summary: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. •Mitochondrial DNAPs harbor amino and carboxyl-terminal extensions that are physically conected•N-terminal deletion of mitochondrial DNA polymerase impinges nucleotide addition and exonucleolysis•A C-terminal deletion mutant is also impaired in nucleotide addition and exonucleolysis
ISSN:1567-7249
1872-8278
1872-8278
DOI:10.1016/j.mito.2019.08.005