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

Authors：Trasvina Arenas, Carlos H; Hoyos Gonzalez, Nallely; Castro Lara, Atzimba Y; Rodriguez Hernandez, Annia; Sanchez Sandoval, Maria E; Jimenez Sandoval, Pedro; Ayala Garcia, Victor M; Diaz Quezada, Corina; Lodi, Tiziana; Baruffini, Enrico; Brieba, Luis G^*

Source：MITOCHONDRION, 2019.

DOI：10.1016/j.mito.2019.08.005

• DNA polymerase
• DNA replication
• Enzyme kinetics
• Mitochondria
• Regulation
• Structure-function

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.