POLG

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List of terms related to POLG

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

DNA polymerase subunit gamma is an enzyme that in humans is encoded by the POLG gene.

Function

POLG is a gene that codes for the catalytic subunit of the mitochondrial DNA polymerase, called DNA polymerase gamma. The human POLG cDNA and gene were cloned and mapped to chromosome band 15q25. In eukaryotic cells, the mitochondrial DNA is replicated by DNA polymerase gamma, a trimeric protein complex composed of a catalytic subunit of 140 kDa encoded by the POLG gene and a dimeric accessory subunit of 55 kDa encoded by the POLG2 gene. 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.

Clinical significance

Mutations in the POLG gene are associated with several mitochondrial diseases, including Alpers' disease, ataxia-neuropathy disorders, and dominant and recessive forms of progressive external ophthalmoplegia. 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.

Further reading

• Graziewicz MA, Longley MJ, Copeland WC (Feb 2006). "DNA polymerase gamma in mitochondrial DNA replication and repair". Chemical Reviews. 106 (2): 383–405. doi:10.1021/cr040463d. PMID 16464011.
• Hudson G, Chinnery PF (Oct 2006). "Mitochondrial DNA polymerase-gamma and human disease". Human Molecular Genetics. 15 Spec No 2: R244–52. doi:10.1093/hmg/ddl233. PMID 16987890.
• Lestienne P (Aug 1987). "Evidence for a direct role of the DNA polymerase gamma in the replication of the human mitochondrial DNA in vitro". Biochemical and Biophysical Research Communications. 146 (3): 1146–53. doi:10.1016/0006-291X(87)90767-4. PMID 3619920.
• Ropp PA, Copeland WC (Sep 1996). "Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase gamma". Genomics. 36 (3): 449–58. doi:10.1006/geno.1996.0490. PMID 8884268.
• Lecrenier N, Van Der Bruggen P, Foury F (Jan 1997). "Mitochondrial DNA polymerases from yeast to man: a new family of polymerases". Gene. 185 (1): 147–52. doi:10.1016/S0378-1119(96)00663-4. PMID 9034326.
• Walker RL, Anziano P, Meltzer PS (Mar 1997). "A PAC containing the human mitochondrial DNA polymerase gamma gene (POLG) maps to chromosome 15q25". Genomics. 40 (2): 376–8. doi:10.1006/geno.1996.4580. PMID 9119411.
• Kapsa RM, Quigley AF, Han TF, Jean-Francois MJ, Vaughan P, Byrne E (Oct 1998). "mtDNA replicative potential remains constant during ageing: polymerase gamma activity does not correlate with age related cytochrome oxidase activity decline in platelets". Nucleic Acids Research. 26 (19): 4365–73. doi:10.1093/nar/26.19.4365. PMC 147866. PMID 9742236.
• Spelbrink JN, Toivonen JM, Hakkaart GA, Kurkela JM, Cooper HM, Lehtinen SK, Lecrenier N, Back JW, Speijer D, Foury F, Jacobs HT (Aug 2000). "In vivo functional analysis of the human mitochondrial DNA polymerase POLG expressed in cultured human cells". The Journal of Biological Chemistry. 275 (32): 24818–28. doi:10.1074/jbc.M000559200. PMID 10827171.
• Van Goethem G, Dermaut B, Löfgren A, Martin JJ, Van Broeckhoven C (Jul 2001). "Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions". Nature Genetics. 28 (3): 211–2. doi:10.1038/90034. PMID 11431686.
• Hirano M, DiMauro S (Dec 2001). "ANT1, Twinkle, POLG, and TP: new genes open our eyes to ophthalmoplegia". Neurology. 57 (12): 2163–5. doi:10.1212/wnl.57.12.2163. PMID 11756592.
• Ponamarev MV, Longley MJ, Nguyen D, Kunkel TA, Copeland WC (May 2002). "Active site mutation in DNA polymerase gamma associated with progressive external ophthalmoplegia causes error-prone DNA synthesis". The Journal of Biological Chemistry. 277 (18): 15225–8. doi:10.1074/jbc.C200100200. PMID 11897778.
• Nitanai Y, Satow Y, Adachi H, Tsujimoto M (Aug 2002). "Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis". Journal of Molecular Biology. 321 (2): 177–84. doi:10.1016/S0022-2836(02)00632-0. PMID 12144777.
• Lamantea E, Tiranti V, Bordoni A, Toscano A, Bono F, Servidei S, Papadimitriou A, Spelbrink H, Silvestri L, Casari G, Comi GP, Zeviani M (Aug 2002). "Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia". Annals of Neurology. 52 (2): 211–9. doi:10.1002/ana.10278. PMID 12210792.
• Van Goethem G, Martin JJ, Dermaut B, Löfgren A, Wibail A, Ververken D, Tack P, Dehaene I, Van Zandijcke M, Moonen M, Ceuterick C, De Jonghe P, Van Broeckhoven C (Feb 2003). "Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia". Neuromuscular Disorders. 13 (2): 133–42. doi:10.1016/S0960-8966(02)00216-X. PMID 12565911.
• Jazayeri M, Andreyev A, Will Y, Ward M, Anderson CM, Clevenger W (Mar 2003). "Inducible expression of a dominant negative DNA polymerase-gamma depletes mitochondrial DNA and produces a rho0 phenotype". The Journal of Biological Chemistry. 278 (11): 9823–30. doi:10.1074/jbc.M211730200. PMID 12645575.
• Garrido N, Griparic L, Jokitalo E, Wartiovaara J, van der Bliek AM, Spelbrink JN (Apr 2003). "Composition and dynamics of human mitochondrial nucleoids". Molecular Biology of the Cell. 14 (4): 1583–96. doi:10.1091/mbc.E02-07-0399. PMC 153124. PMID 12686611.
• Agostino A, Valletta L, Chinnery PF, Ferrari G, Carrara F, Taylor RW, Schaefer AM, Turnbull DM, Tiranti V, Zeviani M (Apr 2003). "Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO)". Neurology. 60 (8): 1354–6. doi:10.1212/01.wnl.0000056088.09408.3c. PMID 12707443.
• Van Goethem G, Schwartz M, Löfgren A, Dermaut B, Van Broeckhoven C, Vissing J (Jul 2003). "Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy". European Journal of Human Genetics. 11 (7): 547–9. doi:10.1038/sj.ejhg.5201002. PMID 12825077.
• Zullo SJ, Butler L, Zahorchak RJ, Macville M, Wilkes C, Merril CR (Mar 1998). "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. doi:10.1159/000134672. PMID 9465903.

External links

• GeneReviews/NCBI/NIH/UW entry on POLG-Related Disorders