Biology:POLG

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

DNA polymerase subunit gamma (POLG or POLG1) is an enzyme that in humans is encoded by the POLG gene.[1] 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).[2]

Structure

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.[3][4] POLG, the protein encoded by this gene, is a member of the DNA polymerase type-A family. It is a mitochondrion nucleoid with an Mg2+ cofactor and 15 turns, 52 beta strands, and 39 alpha helixes.[5][6] 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.[2]

Function

POLG is a gene that codes for the catalytic subunit of the mitochondrial DNA polymerase, called DNA polymerase gamma.[2] The human POLG cDNA and gene were cloned and mapped to chromosome band 15q25.[7] 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.[8] 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. POLG activity is coordinated with mitochondrial SSB activity during DNA replication.[9]

Catalytic activity

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).[5][6]

Clinical significance

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).[2] Pathogenic variants have also been linked with fatal congenital myopathy and gastrointestinal pseudo-obstruction and fatal infantile hepatic failure.[10][11] 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.[12]

Interactions

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.[13]

Notable people

  • Prince Frederick of Luxembourg (2002-2025)[14]

References

  1. ↑ "Localization by fluorescence in situ hybridization (FISH) of human mitochondrial polymerase gamma (POLG) to human chromosome band 15q24→q26, and of mouse mitochondrial polymerase gamma (Polg) to mouse chromosome band 7E, with confirmation by direct sequence analysis of bacterial artificial chromosomes (BACs)". Cytogenetics and Cell Genetics 78 (3–4): 281–4. Mar 1998. doi:10.1159/000134672. PMID 9465903. https://zenodo.org/record/1235426. 
  2. ↑ 2.0 2.1 2.2 2.3 Entrez Gene: POLG polymerase (DNA directed), gamma, catalytic subunitPublic Domain This article incorporates text from this source, which is in the public domain.
  3. ↑ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". https://amino.heartproteome.org/web/protein/Q9U208. 
  4. ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. October 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338. 
  5. ↑ 5.0 5.1 "POLG - DNA polymerase subunit gamma-1 - Homo sapiens (Human) - POLG gene & protein" (in en). https://www.uniprot.org/uniprot/P54098.  This article incorporates text available under the CC BY 4.0 license.
  6. ↑ 6.0 6.1 "UniProt: the universal protein knowledgebase". Nucleic Acids Research 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMID 27899622. 
  7. ↑ "Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase gamma". Genomics 36 (3): 449–58. September 1996. doi:10.1006/geno.1996.0490. PMID 8884268. 
  8. ↑ "DNA polymerase gamma in mitochondrial DNA replication and repair". Chemical Reviews 106 (2): 383–405. February 2006. doi:10.1021/cr040463d. PMID 16464011. 
  9. ↑ Plaza-G.A., Ismael; Lemishko, Kateryna M; Crespo, Rodrigo; Truong, Thinh Q; Kaguni, Laurie S; Cao-García, Francisco J; Ciesielski, Grzegorz L; Ibarra, Borja (2023-02-28). "Mechanism of strand displacement DNA synthesis by the coordinated activities of human mitochondrial DNA polymerase and SSB" (in en). Nucleic Acids Research 51 (4): 1750–1765. doi:10.1093/nar/gkad037. ISSN 0305-1048. PMID 36744436. PMC 9976888. https://academic.oup.com/nar/article/51/4/1750/7028276. 
  10. ↑ "Fatal congenital myopathy and gastrointestinal pseudo-obstruction due to POLG1 mutations". Neurology 72 (12): 1103–5. March 2009. doi:10.1212/01.wnl.0000345002.47396.e1. PMID 19307547. 
  11. ↑ "Mitochondrial DNA depletion and fatal infantile hepatic failure due to mutations in the mitochondrial polymerase γ (POLG) gene: a combined morphological/enzyme histochemical and immunocytochemical/biochemical and molecular genetic study". Journal of Cellular and Molecular Medicine 15 (2): 445–56. February 2011. doi:10.1111/j.1582-4934.2009.00819.x. PMID 19538466. 
  12. ↑ "Mitochondrial point mutations do not limit the natural lifespan of mice". Nature Genetics 39 (4): 540–3. April 2007. doi:10.1038/ng1988. PMID 17334366. 
  13. ↑ "50 binary interactions found for search term POLG". IntAct Molecular Interaction Database. EMBL-EBI. https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=POLG. 
  14. ↑ Magramo, Michael Rios, Kathleen (2025-03-10). "Prince Frederik of Luxembourg dies from rare disease" (in en). https://www.cnn.com/2025/03/09/europe/prince-frederik-luxembourg-dies-polg-intl-latam. 

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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