DNA polymerase subunit gamma (POLG or POLG1) is an enzyme that in humans is encoded by the POLG gene.^[5] Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE).^[6]

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POLG
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3IKM, 4ZTU, 4ZTZ, 5C53, 5C52, 5C51
Identifiers
Aliases	POLG, MDP1, MIRAS, MTDPS4A, MTDPS4B, PEO, POLG1, POLGA, SANDO, SCAE, polymerase (DNA) gamma, catalytic subunit, DNA polymerase gamma, catalytic subunit, ORF-Y, POLGARF
External IDs	OMIM: 174763; MGI: 1196389; HomoloGene: 2016; GeneCards: POLG; OMA:POLG - orthologs
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q26.1 Start 89,305,198 bp[1] End 89,334,861 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 D2 Start 79,095,979 bp[2] End 79,116,110 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibial nerve transverse colon body of stomach right lobe of thyroid gland body of pancreas spleen minor salivary glands cardia skin of abdomen fundus Top expressed in spermatocyte spermatid yolk sac superior frontal gyrus thymus seminiferous tubule lip cerebellar cortex renal corpuscle primitive streak More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding transferase activity 3'-5' exonuclease activity nucleotidyltransferase activity chromatin binding protease binding DNA binding DNA-directed DNA polymerase activity Cellular component terminal bouton gamma DNA polymerase complex mitochondrial nucleoid mitochondrion protein-containing complex Biological process DNA replication response to gamma radiation cellular response to glucose stimulus DNA metabolic process response to light stimulus DNA-dependent DNA replication human ageing response to hyperoxia base-excision repair, gap-filling nucleic acid phosphodiester bond hydrolysis DNA biosynthetic process mitochondrial DNA replication Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5428 18975 Ensembl ENSG00000140521 ENSMUSG00000039176 UniProt P54098 P54099 RefSeq (mRNA) NM_002693 NM_001126131 NM_017462 NM_001360095 NM_001360096 RefSeq (protein) NP_001119603 NP_002684 n/a Location (UCSC) Chr 15: 89.31 – 89.33 Mb Chr 7: 79.1 – 79.12 Mb PubMed search [3] [4]
Wikidata
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POLG is located on the q arm of chromosome 15 in position 26.1 and has 23 exons. The POLG gene produces a 140 kDa protein composed of 1239 amino acids.^[7][8] POLG, the protein encoded by this gene, is a member of the DNA polymerase type-A family. It is a mitochondrion nucleiod with an Mg2+ cofactor and 15 turns, 52 beta strands, and 39 alpha helixes.^[9][10] POLG contains a polyglutamine tract near its N-terminus that may be polymorphic. Two transcript variants encoding the same protein have been found for this gene.^[6]

POLG is a gene that codes for the catalytic subunit of the mitochondrial DNA polymerase, called DNA polymerase gamma.^[6] The human POLG cDNA and gene were cloned and mapped to chromosome band 15q25.^[11] In eukaryotic cells, the mitochondrial DNA is replicated by DNA polymerase gamma, a trimeric protein complex composed of a catalytic subunit, POLG, and a dimeric accessory subunit of 55 kDa encoded by the POLG2 gene.^[12] The catalytic subunit contains three enzymatic activities, a DNA polymerase activity, a 3’-5’ exonuclease activity that proofreads misincorporated nucleotides, and a 5’-dRP lyase activity required for base excision repair.

Mutations in the POLG gene are associated with several mitochondrial diseases, progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE).^[6] Pathogenic variants have also been linked with fatal congenital myopathy and gastrointestinal pseudo-obstruction and fatal infantile hepatic failure.^[13][14] A list of all published mutations in the POLG coding region and their associated disease can be found at the Human DNA Polymerase Gamma Mutation Database.

Mice heterozygous for a Polg mutation are only able to replicate their mitochondrial DNA inaccurately, so that they sustain a 500-fold higher mutation burden than normal mice. These mice show no clear features of rapidly accelerated aging, indicating that mitochondrial mutations do not have a causal role in natural aging.^[15]

POLG has been shown to have 50 binary protein-protein interactions including 32 co-complex interactions. POLG appears to interact with POLG2, Dlg4, Tp53, and Sod2.^[16]