POLG

From Wikipedia, the free encyclopedia
Polymerase (DNA directed), gamma
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsPOLG; MDP1; MIRAS; MTDPS4A; MTDPS4B; PEO; POLG1; POLGA; SANDO; SCAE
External IDsOMIM: 174763 MGI: 1196389 HomoloGene: 2016 ChEMBL: 2732 GeneCards: POLG Gene
EC number2.7.7.7
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez542818975
EnsemblENSG00000140521ENSMUSG00000039176
UniProtP54098P54099
RefSeq (mRNA)NM_001126131NM_017462
RefSeq (protein)NP_001119603NP_059490
Location (UCSC)Chr 15:
89.86 – 89.88 Mb		Chr 7:
79.45 – 79.47 Mb
PubMed search
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DNA polymerase subunit gamma is an enzyme that in humans is encoded by the POLG gene.[1]

Functions

POLG (alias, POLG1 or POLGa) is the gene that codes for the catalytic subunit of the mitochondrial DNA polymerase, called DNA polymerase gamma.[2] The human POLG cDNA and gene were originally cloned mapped to chromosome 15, 15,q25.[3] 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.[4] 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

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 lists all published mutations in the POLG coding region and their associated disease can be found at the Human DNA Polymerase Gamma Mutation Database.

References

  1. ↑ 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)". Cytogenet Cell Genet 78 (3–4): 281–4. doi:10.1159/000134672. PMID 9465903. 
  2. ↑ Entrez Gene: POLG polymerase (DNA directed), gamma, catalytic subunit
  3. ↑ Ropp, PA, Copeland, WC (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. 
  4. ↑ Graziewicz, MA, Longley, MJ, Copeland, WC (2006). "DNA polymerase gamma in mitochondrial DNA replication and repair.". Chem. Rev. 106 (2): 383–405. doi:10.1021/cr040463d. PMID 16464011. 

External links

Further reading

  • Graziewicz MA, Longley MJ, Copeland WC (2006). "DNA polymerase gamma in mitochondrial DNA replication and repair". Chem. Rev. 106 (2): 383–405. doi:10.1021/cr040463d. PMID 16464011. 
  • Hudson G, Chinnery PF (2006). "Mitochondrial DNA polymerase-gamma and human disease". Hum. Mol. Genet. 15 Spec No 2: R244–52. doi:10.1093/hmg/ddl233. PMID 16987890. 
  • Lestienne P (1987). "Evidence for a direct role of the DNA polymerase gamma in the replication of the human mitochondrial DNA in vitro". Biochem. Biophys. Res. Commun. 146 (3): 1146–53. doi:10.1016/0006-291X(87)90767-4. PMID 3619920. 
  • Ropp PA, Copeland WC (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 (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 (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, et al. (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 Res. 26 (19): 4365–73. doi:10.1093/nar/26.19.4365. PMC 147866. PMID 9742236. 
  • Spelbrink JN, Toivonen JM, Hakkaart GA, et al. (2000). "In vivo functional analysis of the human mitochondrial DNA polymerase POLG expressed in cultured human cells". J. Biol. Chem. 275 (32): 24818–28. doi:10.1074/jbc.M000559200. PMID 10827171. 
  • Van Goethem G, Dermaut B, Löfgren A, et al. (2001). "Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions". Nat. Genet. 28 (3): 211–2. doi:10.1038/90034. PMID 11431686. 
  • Hirano M, DiMauro S (2003). "ANT1, Twinkle, POLG, and TP: new genes open our eyes to ophthalmoplegia". Neurology 57 (12): 2163–5. PMID 11756592. 
  • Ponamarev MV, Longley MJ, Nguyen D, et al. (2002). "Active site mutation in DNA polymerase gamma associated with progressive external ophthalmoplegia causes error-prone DNA synthesis". J. Biol. Chem. 277 (18): 15225–8. doi:10.1074/jbc.C200100200. PMID 11897778. 
  • Nitanai Y, Satow Y, Adachi H, Tsujimoto M (2002). "Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis". J. Mol. Biol. 321 (2): 177–84. doi:10.1016/S0022-2836(02)00632-0. PMID 12144777. 
  • Lamantea E, Tiranti V, Bordoni A, et al. (2002). "Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia". Ann. Neurol. 52 (2): 211–9. doi:10.1002/ana.10278. PMID 12210792. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
  • Van Goethem G, Martin JJ, Dermaut B, et al. (2003). "Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia". Neuromuscul. Disord. 13 (2): 133–42. doi:10.1016/S0960-8966(02)00216-X. PMID 12565911. 
  • Jazayeri M, Andreyev A, Will Y, et al. (2003). "Inducible expression of a dominant negative DNA polymerase-gamma depletes mitochondrial DNA and produces a rho0 phenotype". J. Biol. Chem. 278 (11): 9823–30. doi:10.1074/jbc.M211730200. PMID 12645575. 
  • Garrido N, Griparic L, Jokitalo E, et al. (2003). "Composition and Dynamics of Human Mitochondrial Nucleoids". Mol. Biol. Cell 14 (4): 1583–96. doi:10.1091/mbc.E02-07-0399. PMC 153124. PMID 12686611. 
  • Agostino A, Valletta L, Chinnery PF, et al. (2004). "Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO)". Neurology 60 (8): 1354–6. PMID 12707443. 
  • Van Goethem G, Schwartz M, Löfgren A, et al. (2004). "Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy". Eur. J. Hum. Genet. 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)". Cytogenet Cell Genet 78 (3–4): 281–4. doi:10.1159/000134672. PMID 9465903. 


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