POLG
POLG (DNA polymerase gamma, catalytic subunit; also POLG1 or POLGA) is the catalytic subunit of the mitochondrial DNA polymerase and is solely responsible for replicating mitochondrial DNA (mtDNA). It combines 5' to 3' polymerase activity with 3' to 5' proofreading exonuclease activity. Browse Assay Genie's current range of POLG research reagents below, or read on for the biology behind the target.
POLG replicates both the heavy and light strands of the circular mtDNA genome. It uses a single-stranded DNA template, RNA primers and the four deoxyribonucleoside triphosphates as substrates. At the replication fork it functionally interacts with TWNK and SSBP1 to form a highly processive replisome. TWNK unwinds the double-stranded template, and SSBP1 covers the parental heavy strand so that the whole mitochondrial genome can be copied continuously. Each nucleotide incorporation cycle involves binding of the incoming nucleotide, phosphodiester bond formation that extends the primer 3' end, and translocation of the primer terminus.
The enzyme is highly accurate because of high nucleotide selectivity and 3' to 5' exonucleolytic proofreading. When a misincorporation occurs, POLG switches from replication to an editing mode and removes the wrong nucleoside in the exonuclease active site through an SN2 mechanism, in which Asp-198 catalyses hydrolysis and Glu-200 stabilises the leaving group. Proofreading is weaker across longer homopolymeric stretches. POLG also has 5'-deoxyribose phosphate lyase activity and fills gaps during base-excision repair of mtDNA, releasing the sugar moiety from incised apurinic/apyrimidinic sites to produce a substrate for DNA ligase.
POLG belongs to the DNA polymerase type-A family. The mitochondrial DNA polymerase is a heterotrimer: this catalytic subunit plus a homodimer of accessory subunits. The protein carries a possibly polymorphic polyglutamine tract near its N-terminus, and two transcript variants encode the same protein. Defects in the POLG gene cause progressive external ophthalmoplegia with mtDNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Mouse and rat both have a Polg ortholog.
POLG is the sole polymerase that replicates mtDNA, working with TWNK and SSBP1 in a processive replisome.
Its proofreading exonuclease and dRP lyase activities make it central to mtDNA accuracy and base-excision repair gap filling.
Defects in POLG underlie PEOA1, SANDO, Alpers-Huttenlocher syndrome and MNGIE.
As a type-A family polymerase with separate polymerase and exonuclease sites, POLG is a model for studying nucleotide selectivity and editing.
POLG is the catalytic subunit of DNA polymerase gamma and is solely responsible for replicating mitochondrial DNA. It extends primers with 5' to 3' polymerase activity, proofreads errors by 3' to 5' exonuclease activity, and fills gaps during base-excision repair through its dRP lyase function.
POLG is also known as POLG1 and POLGA. Earlier names include polymerase (DNA directed), gamma and polymerase (DNA) gamma, catalytic subunit. UniProt lists the protein as DNA polymerase subunit gamma-1. Two transcript variants encode the same protein.
Defects in POLG cause PEOA1, SANDO, Alpers-Huttenlocher syndrome and MNGIE. Mouse and rat each have an ortholog named Polg. Check the datasheet of any product for its validated reactivity.
Replisome partners, other mitochondrial DNA maintenance proteins and related targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P54098; product specifications from Assay Genie datasheets.