POLG

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Polymerase (DNA directed), gamma
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols POLG ; MDP1; MIRAS; MTDPS4A; MTDPS4B; PEO; POLG1; POLGA; SANDO; SCAE
External IDs OMIM174763 MGI1196389 HomoloGene2016 ChEMBL: 2732 GeneCards: POLG Gene
EC number 2.7.7.7
RNA expression pattern
PBB GE POLG 203366 at tn.png
PBB GE POLG 217635 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5428 18975
Ensembl ENSG00000140521 ENSMUSG00000039176
UniProt P54098 P54099
RefSeq (mRNA) NM_001126131 NM_017462
RefSeq (protein) NP_001119603 NP_059490
Location (UCSC) Chr 15:
89.32 – 89.33 Mb
Chr 7:
79.45 – 79.47 Mb
PubMed search [1] [2]

DNA polymerase subunit gamma is an enzyme that in humans is encoded by the POLG gene.[1]

Function[edit]

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.[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.

Clinical significance[edit]

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.

References[edit]

  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)". Cytogenetics and Cell Genetics 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 (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. 
  4. ^ 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. 

Further reading[edit]

  • 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 et al. (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 et al. (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 et al. (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 et al. (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[edit]