POLG is located on theq arm of chromosome 15 in position 26.1 and has 23exons. ThePOLG gene produces a 140 kDa protein composed of 1239amino acids.[7][8] POLG, theprotein encoded by this gene, is a member of the DNA polymerase type-A family. It is a mitochondrion nucleoid with anMg2+ cofactor and 15 turns, 52beta strands, and 39alpha helixes.[9][10] POLG contains apolyglutamine tract near itsN-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 mitochondrialDNA polymerase, called DNA polymerase gamma.[6] The humanPOLG cDNA and gene were cloned and mapped to chromosome band 15q25.[11] Ineukaryotic cells, themitochondrial 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 thePOLG2 gene.[12] The catalytic subunit contains three enzymatic activities, a DNA polymerase activity, a 3’-5’ exonuclease activity that proofreads misincorporatednucleotides, and a 5’-dRPlyase activity required forbase excision repair.
Mice heterozygous for aPolgmutation are only able to replicate theirmitochondrial 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 naturalaging.[15]
^Ropp PA, Copeland WC (September 1996). "Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase gamma".Genomics.36 (3):449–58.doi:10.1006/geno.1996.0490.PMID8884268.
^Graziewicz MA, Longley MJ, Copeland WC (February 2006). "DNA polymerase gamma in mitochondrial DNA replication and repair".Chemical Reviews.106 (2):383–405.doi:10.1021/cr040463d.PMID16464011.
^Vermulst M, Bielas JH, Kujoth GC, Ladiges WC, Rabinovitch PS, Prolla TA, Loeb LA (April 2007). "Mitochondrial point mutations do not limit the natural lifespan of mice".Nature Genetics.39 (4):540–3.doi:10.1038/ng1988.PMID17334366.S2CID291780.
Lestienne P (August 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.PMID3619920.
Ropp PA, Copeland WC (September 1996). "Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase gamma".Genomics.36 (3):449–58.doi:10.1006/geno.1996.0490.PMID8884268.
Lecrenier N, Van Der Bruggen P, Foury F (January 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.PMID9034326.
Van Goethem G, Dermaut B, Löfgren A, Martin JJ, Van Broeckhoven C (July 2001). "Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions".Nature Genetics.28 (3):211–2.doi:10.1038/90034.PMID11431686.S2CID35417835.
Nitanai Y, Satow Y, Adachi H, Tsujimoto M (August 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.PMID12144777.
Lamantea E, Tiranti V, Bordoni A, Toscano A, Bono F, Servidei S, Papadimitriou A, Spelbrink H, Silvestri L, Casari G, Comi GP, Zeviani M (August 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.PMID12210792.S2CID8324826.
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 (February 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.PMID12565911.S2CID2159997.
Agostino A, Valletta L, Chinnery PF, Ferrari G, Carrara F, Taylor RW, Schaefer AM, Turnbull DM, Tiranti V, Zeviani M (April 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.PMID12707443.S2CID31209510.
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