PolG2 encodes the accessory (beta) subunit of mitochondrial DNA polymerase gamma, a 35 kDa protein structurally related to class II aminoacyl-tRNA synthetases that heterodimerizes with the catalytic subunit PolG1 (tamas) through multiple contacts with its exonuclease and spacer regions. PolG2 does not itself contact DNA in the holoenzyme but raises the catalytic efficiency and processivity of PolG1 roughly fifty-fold. Null mutants lose mtDNA and mitochondrial mass, show reduced cell proliferation in the central nervous system and die at early pupation, establishing PolG2 as essential for mtDNA replication and maintenance.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003727 single-stranded RNA binding | IDA PMID:11294646 Multiple regions of subunit interaction in Drosophila mitoch... | UNDECIDED | Summary: Single-stranded RNA binding (IDA). Reason: The cached abstract of PMID:11294646 only mentions a proposed role of the accessory-subunit C terminus in RNA primer recognition, and an earlier crosslinking study found that the beta subunit does not contact DNA in the holoenzyme. Without the full text the nucleic-acid binding evidence cannot be evaluated; deferring to the curator but not treating it as core. Supporting Evidence: PMID:11294646 the proposed function of the C-terminus of the accessory subunit in RNA primer recognition PMID:7499423 the alpha but not the beta subunit of mitochondrial DNA polymerase makes close contact with DNA |
| GO:0005515 protein binding | IPI PMID:11294646 Multiple regions of subunit interaction in Drosophila mitoch... | REMOVE | Summary: Protein binding (IPI) with PolG1. Reason: The partner is the catalytic subunit PolG1 (GOA WITH/FROM UniProtKB:Q27607); this subunit contact is already captured by part_of GO:0005760 gamma DNA polymerase complex, and bare protein binding adds no functional information. |
| GO:0005515 protein binding | IPI PMID:15537632 Mutations in the spacer region of Drosophila mitochondrial D... | REMOVE | Summary: Protein binding (IPI) with PolG1. Reason: The partner is the catalytic subunit PolG1 (GOA WITH/FROM UniProtKB:Q27607); this subunit contact is already captured by part_of GO:0005760 gamma DNA polymerase complex, and bare protein binding adds no functional information. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Cytoplasm (IBA). Reason: IBA from the root of the glycyl-tRNA synthetase/Pol gamma accessory subunit family (PTN000078673), whose donors are mostly cytoplasmic glycyl-tRNA synthetases (e.g. AT1G29880, SGD:S000000325, P41250). PolG2 diverged from the aminoacyl-tRNA synthetase ancestor to become a mitochondrial matrix polymerase subunit with a mitochondrial presequence; cytoplasm is at most a transient precursor location (or the heterologous Sf9 reconstitution), not where it is active. Supporting Evidence: PMID:10506144 Recombinant heterodimeric holoenzyme was reconstituted in both the mitochondria and cytoplasm of Sf9 cells and required the mitochondrial presequences in both subunits |
| GO:0005739 mitochondrion | IDA PMID:10506144 Baculovirus expression reconstitutes Drosophila mitochondria... | ACCEPT | Summary: Mitochondrion. Reason: PolG2 is imported into mitochondria with PolG1 as the Pol gamma holoenzyme. Supporting Evidence: PMID:10506144 Recombinant heterodimeric holoenzyme was reconstituted in both the mitochondria and cytoplasm of Sf9 cells and required the mitochondrial presequences in both subunits |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrion (IEA). Reason: Consistent with experimental evidence. Supporting Evidence: file:DROME/PolG2/PolG2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:9153213} |
| GO:0005739 mitochondrion | IPI PMID:9153213 Accessory subunit of mitochondrial DNA polymerase from Droso... | ACCEPT | Summary: Mitochondrion. Reason: Subunit-specific antisera immunoprecipitate the native mitochondrial enzyme containing both subunits. Supporting Evidence: PMID:9153213 Demonstration of the physical association of the two subunits in the Drosophila enzyme |
| GO:0005759 mitochondrial matrix | NAS PMID:15537632 Mutations in the spacer region of Drosophila mitochondrial D... | ACCEPT | Summary: Mitochondrial matrix (NAS). Reason: Pol gamma acts on mtDNA in the matrix. Supporting Evidence: PMID:15537632 mutations in three of the four conserved sequence elements within the spacer alter enzyme activity, processivity, and/or DNA binding affinity |
| GO:0005760 gamma DNA polymerase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Gamma DNA polymerase complex (IBA). Reason: IBA donors are human POLG2 (Q9UHN1), Xenopus polg2 and fly PolG2 itself; consistent with direct evidence. Supporting Evidence: PMID:9153213 Demonstration of the physical association of the two subunits in the Drosophila enzyme |
| GO:0005760 gamma DNA polymerase complex | IDA PMID:10506144 Baculovirus expression reconstitutes Drosophila mitochondria... | ACCEPT | Summary: Accessory subunit of the gamma DNA polymerase complex. Reason: Pol gamma is a heterodimer of the catalytic subunit PolG1 and the 35 kDa accessory subunit PolG2. Supporting Evidence: PMID:10506144 This provides evidence of a critical role for the accessory subunit in the catalytic efficiency of Drosophila mitochondrial DNA polymerase |
| GO:0005760 gamma DNA polymerase complex | IDA PMID:11294646 Multiple regions of subunit interaction in Drosophila mitoch... | ACCEPT | Summary: Accessory subunit of the gamma DNA polymerase complex. Reason: Pol gamma is a heterodimer of the catalytic subunit PolG1 and the 35 kDa accessory subunit PolG2. Supporting Evidence: PMID:11294646 The M and C regions comprise the major contacts involved in subunit interaction |
| GO:0005760 gamma DNA polymerase complex | IDA PMID:15537632 Mutations in the spacer region of Drosophila mitochondrial D... | ACCEPT | Summary: Accessory subunit of the gamma DNA polymerase complex. Reason: Pol gamma is a heterodimer of the catalytic subunit PolG1 and the 35 kDa accessory subunit PolG2. Supporting Evidence: PMID:15537632 The catalytic subunit (alpha) of mitochondrial DNA polymerase (pol gamma) |
| GO:0005760 gamma DNA polymerase complex | IDA PMID:26446790 Mitochondrial Single-stranded DNA-binding Proteins Stimulate... | ACCEPT | Summary: Accessory subunit of the gamma DNA polymerase complex. Reason: Pol gamma is a heterodimer of the catalytic subunit PolG1 and the 35 kDa accessory subunit PolG2. Supporting Evidence: PMID:26446790 The activity of the mitochondrial replicase, DNA polymerase Ξ³ (Pol Ξ³) is stimulated by another key component of the mitochondrial replisome, the mitochondrial single-stranded DNA-binding protein (mtSSB) |
| GO:0005760 gamma DNA polymerase complex | IDA PMID:3095323 A mitochondrial DNA polymerase from embryos of Drosophila me... | ACCEPT | Summary: Accessory subunit of the gamma DNA polymerase complex. Reason: Pol gamma is a heterodimer of the catalytic subunit PolG1 and the 35 kDa accessory subunit PolG2. Supporting Evidence: PMID:3095323 the data suggest that the D. melanogaster DNA polymerase gamma is a heterodimer |
| GO:0005760 gamma DNA polymerase complex | IDA PMID:7499423 Subunit structure of mitochondrial DNA polymerase from Droso... | ACCEPT | Summary: Accessory subunit of the gamma DNA polymerase complex. Reason: Pol gamma is a heterodimer of the catalytic subunit PolG1 and the 35 kDa accessory subunit PolG2. Supporting Evidence: PMID:7499423 provide strong evidence for the physical association of the 3'-->5' exonuclease with the two subunit enzyme |
| GO:0005760 gamma DNA polymerase complex | IPI PMID:15537632 Mutations in the spacer region of Drosophila mitochondrial D... | ACCEPT | Summary: Accessory subunit of the gamma DNA polymerase complex. Reason: Pol gamma is a heterodimer of the catalytic subunit PolG1 and the 35 kDa accessory subunit PolG2. Supporting Evidence: PMID:15537632 The catalytic subunit (alpha) of mitochondrial DNA polymerase (pol gamma) |
| GO:0005760 gamma DNA polymerase complex | IPI PMID:9153213 Accessory subunit of mitochondrial DNA polymerase from Droso... | ACCEPT | Summary: Accessory subunit of the gamma DNA polymerase complex. Reason: Pol gamma is a heterodimer of the catalytic subunit PolG1 and the 35 kDa accessory subunit PolG2. Supporting Evidence: PMID:9153213 Demonstration of the physical association of the two subunits in the Drosophila enzyme |
| GO:0006261 DNA-templated DNA replication | IDA PMID:10329675 Functional interactions of mitochondrial DNA polymerase and ... | MODIFY | Summary: DNA-templated DNA replication (IDA). Reason: In vitro DNA synthesis by the purified heterodimer; correct but less specific than GO:0006264 mitochondrial DNA replication, which the gene already carries. Proposed replacements: mitochondrial DNA replication Supporting Evidence: PMID:3142517 the catalytic properties of the near-homogeneous Drosophila DNA polymerase gamma are consistent with the in vivo requirements for mitochondrial DNA synthesis |
| GO:0006261 DNA-templated DNA replication | IDA PMID:11294646 Multiple regions of subunit interaction in Drosophila mitoch... | MODIFY | Summary: DNA-templated DNA replication (IDA). Reason: In vitro DNA synthesis by the purified heterodimer; correct but less specific than GO:0006264 mitochondrial DNA replication, which the gene already carries. Proposed replacements: mitochondrial DNA replication Supporting Evidence: PMID:3142517 the catalytic properties of the near-homogeneous Drosophila DNA polymerase gamma are consistent with the in vivo requirements for mitochondrial DNA synthesis |
| GO:0006261 DNA-templated DNA replication | IDA PMID:1429661 3'-->5' exonuclease in Drosophila mitochondrial DNA polymera... | MODIFY | Summary: DNA-templated DNA replication (IDA). Reason: In vitro DNA synthesis by the purified heterodimer; correct but less specific than GO:0006264 mitochondrial DNA replication, which the gene already carries. Proposed replacements: mitochondrial DNA replication Supporting Evidence: PMID:3142517 the catalytic properties of the near-homogeneous Drosophila DNA polymerase gamma are consistent with the in vivo requirements for mitochondrial DNA synthesis |
| GO:0006261 DNA-templated DNA replication | IDA PMID:14754882 Physiological and biochemical defects in functional interact... | MODIFY | Summary: DNA-templated DNA replication (IDA). Reason: In vitro DNA synthesis by the purified heterodimer; correct but less specific than GO:0006264 mitochondrial DNA replication, which the gene already carries. Proposed replacements: mitochondrial DNA replication Supporting Evidence: PMID:3142517 the catalytic properties of the near-homogeneous Drosophila DNA polymerase gamma are consistent with the in vivo requirements for mitochondrial DNA synthesis |
| GO:0006261 DNA-templated DNA replication | IDA PMID:15537632 Mutations in the spacer region of Drosophila mitochondrial D... | MODIFY | Summary: DNA-templated DNA replication (IDA). Reason: In vitro DNA synthesis by the purified heterodimer; correct but less specific than GO:0006264 mitochondrial DNA replication, which the gene already carries. Proposed replacements: mitochondrial DNA replication Supporting Evidence: PMID:3142517 the catalytic properties of the near-homogeneous Drosophila DNA polymerase gamma are consistent with the in vivo requirements for mitochondrial DNA synthesis |
| GO:0006261 DNA-templated DNA replication | IDA PMID:2671990 Mismatch-specific 3'----5' exonuclease associated with the m... | MODIFY | Summary: DNA-templated DNA replication (IDA). Reason: In vitro DNA synthesis by the purified heterodimer; correct but less specific than GO:0006264 mitochondrial DNA replication, which the gene already carries. Proposed replacements: mitochondrial DNA replication Supporting Evidence: PMID:3142517 the catalytic properties of the near-homogeneous Drosophila DNA polymerase gamma are consistent with the in vivo requirements for mitochondrial DNA synthesis |
| GO:0006261 DNA-templated DNA replication | IDA PMID:3142517 Mitochondrial DNA polymerase from Drosophila melanogaster em... | MODIFY | Summary: DNA-templated DNA replication (IDA). Reason: In vitro DNA synthesis by the purified heterodimer; correct but less specific than GO:0006264 mitochondrial DNA replication, which the gene already carries. Proposed replacements: mitochondrial DNA replication Supporting Evidence: PMID:3142517 the catalytic properties of the near-homogeneous Drosophila DNA polymerase gamma are consistent with the in vivo requirements for mitochondrial DNA synthesis |
| GO:0006261 DNA-templated DNA replication | IDA PMID:7822323 Stimulation of Drosophila mitochondrial DNA polymerase by si... | MODIFY | Summary: DNA-templated DNA replication (IDA). Reason: In vitro DNA synthesis by the purified heterodimer; correct but less specific than GO:0006264 mitochondrial DNA replication, which the gene already carries. Proposed replacements: mitochondrial DNA replication Supporting Evidence: PMID:3142517 the catalytic properties of the near-homogeneous Drosophila DNA polymerase gamma are consistent with the in vivo requirements for mitochondrial DNA synthesis |
| GO:0006261 DNA-templated DNA replication | IDA PMID:8227047 Processivity of mitochondrial DNA polymerase from Drosophila... | MODIFY | Summary: DNA-templated DNA replication (IDA). Reason: In vitro DNA synthesis by the purified heterodimer; correct but less specific than GO:0006264 mitochondrial DNA replication, which the gene already carries. Proposed replacements: mitochondrial DNA replication Supporting Evidence: PMID:3142517 the catalytic properties of the near-homogeneous Drosophila DNA polymerase gamma are consistent with the in vivo requirements for mitochondrial DNA synthesis |
| GO:0006264 mitochondrial DNA replication | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial DNA replication (IBA). Reason: IBA donors human POLG2, mouse Polg2 and fly PolG2; consistent with direct genetic evidence. Supporting Evidence: PMID:11917141 Mutations in the accessory subunit cause lethality during early pupation, concomitant with loss of mtDNA and mitochondrial mass |
| GO:0006264 mitochondrial DNA replication | IDA PMID:10506144 Baculovirus expression reconstitutes Drosophila mitochondria... | ACCEPT | Summary: Mitochondrial DNA replication. Reason: As the accessory subunit of the mitochondrial replicase, PolG2 is required for efficient mtDNA synthesis; null mutants lose mtDNA. Supporting Evidence: PMID:10506144 This provides evidence of a critical role for the accessory subunit in the catalytic efficiency of Drosophila mitochondrial DNA polymerase |
| GO:0006264 mitochondrial DNA replication | IDA PMID:26446790 Mitochondrial Single-stranded DNA-binding Proteins Stimulate... | ACCEPT | Summary: Mitochondrial DNA replication. Reason: As the accessory subunit of the mitochondrial replicase, PolG2 is required for efficient mtDNA synthesis; null mutants lose mtDNA. Supporting Evidence: PMID:26446790 The activity of the mitochondrial replicase, DNA polymerase Ξ³ (Pol Ξ³) is stimulated by another key component of the mitochondrial replisome, the mitochondrial single-stranded DNA-binding protein (mtSSB) |
| GO:0006264 mitochondrial DNA replication | IDA PMID:3095323 A mitochondrial DNA polymerase from embryos of Drosophila me... | ACCEPT | Summary: Mitochondrial DNA replication. Reason: As the accessory subunit of the mitochondrial replicase, PolG2 is required for efficient mtDNA synthesis; null mutants lose mtDNA. Supporting Evidence: PMID:3095323 the catalytic properties of the near-homogeneous Drosophila enzyme are consistent with those of DNA polymerase gamma |
| GO:0006264 mitochondrial DNA replication | IDA PMID:7499423 Subunit structure of mitochondrial DNA polymerase from Droso... | ACCEPT | Summary: Mitochondrial DNA replication. Reason: As the accessory subunit of the mitochondrial replicase, PolG2 is required for efficient mtDNA synthesis; null mutants lose mtDNA. Supporting Evidence: PMID:7499423 provide strong evidence for the physical association of the 3'-->5' exonuclease with the two subunit enzyme |
| GO:0006264 mitochondrial DNA replication | IMP PMID:11917141 The accessory subunit of DNA polymerase gamma is essential f... | ACCEPT | Summary: Mitochondrial DNA replication. Reason: As the accessory subunit of the mitochondrial replicase, PolG2 is required for efficient mtDNA synthesis; null mutants lose mtDNA. Supporting Evidence: PMID:11917141 Mutations in the accessory subunit cause lethality during early pupation, concomitant with loss of mtDNA and mitochondrial mass |
| GO:0006264 mitochondrial DNA replication | IMP PMID:19924234 Disruption of mitochondrial DNA replication in Drosophila in... | ACCEPT | Summary: Mitochondrial DNA replication. Reason: As the accessory subunit of the mitochondrial replicase, PolG2 is required for efficient mtDNA synthesis; null mutants lose mtDNA. Supporting Evidence: PMID:19924234 mutations in pol gamma deplete mtDNA levels |
| GO:0006264 mitochondrial DNA replication | IPI PMID:9153213 Accessory subunit of mitochondrial DNA polymerase from Droso... | ACCEPT | Summary: Mitochondrial DNA replication. Reason: As the accessory subunit of the mitochondrial replicase, PolG2 is required for efficient mtDNA synthesis; null mutants lose mtDNA. Supporting Evidence: PMID:9153213 Demonstration of the physical association of the two subunits in the Drosophila enzyme |
| GO:0006264 mitochondrial DNA replication | NAS PMID:15537632 Mutations in the spacer region of Drosophila mitochondrial D... | ACCEPT | Summary: Mitochondrial DNA replication. Reason: As the accessory subunit of the mitochondrial replicase, PolG2 is required for efficient mtDNA synthesis; null mutants lose mtDNA. Supporting Evidence: PMID:15537632 mutations in three of the four conserved sequence elements within the spacer alter enzyme activity, processivity, and/or DNA binding affinity |
| GO:0030337 DNA polymerase processivity factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: DNA polymerase processivity factor activity. Reason: The accessory subunit increases catalytic efficiency and processivity of the catalytic subunit (50-fold lower specific activity of the catalytic core alone in the fly enzyme). The ISS/IBA transfer from human POLG2 is sound; the fly protein is a monomeric accessory subunit rather than the mammalian dimer. Supporting Evidence: PMID:10506144 This provides evidence of a critical role for the accessory subunit in the catalytic efficiency of Drosophila mitochondrial DNA polymerase PMID:19858216 the dimeric mammalian proteins confer additional processivity to the holoenzyme polymerase |
| GO:0030337 DNA polymerase processivity factor activity | ISS PMID:19858216 Each monomer of the dimeric accessory protein for human mito... | ACCEPT | Summary: DNA polymerase processivity factor activity. Reason: The accessory subunit increases catalytic efficiency and processivity of the catalytic subunit (50-fold lower specific activity of the catalytic core alone in the fly enzyme). The ISS/IBA transfer from human POLG2 is sound; the fly protein is a monomeric accessory subunit rather than the mammalian dimer. Supporting Evidence: PMID:10506144 This provides evidence of a critical role for the accessory subunit in the catalytic efficiency of Drosophila mitochondrial DNA polymerase PMID:19858216 the dimeric mammalian proteins confer additional processivity to the holoenzyme polymerase |
| GO:0071667 DNA/RNA hybrid binding | IDA PMID:11294646 Multiple regions of subunit interaction in Drosophila mitoch... | UNDECIDED | Summary: DNA/RNA hybrid binding (IDA). Reason: The cached abstract of PMID:11294646 only mentions a proposed role of the accessory-subunit C terminus in RNA primer recognition, and an earlier crosslinking study found that the beta subunit does not contact DNA in the holoenzyme. Without the full text the nucleic-acid binding evidence cannot be evaluated; deferring to the curator but not treating it as core. Supporting Evidence: PMID:11294646 the proposed function of the C-terminus of the accessory subunit in RNA primer recognition PMID:7499423 the alpha but not the beta subunit of mitochondrial DNA polymerase makes close contact with DNA |
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Download this section (compressed HTML)Q: Does the Drosophila PolG2 C-terminal domain bind RNA primers or DNA/RNA hybrids at the mtDNA origin, given that it does not contact DNA in the holoenzyme?
Experiment: Measure processivity and primer-template affinity of reconstituted fly Pol gamma with wild-type versus C-terminal-truncated PolG2 on DNA- and RNA-primed templates.
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Download this section (compressed HTML)DNA polymerase gamma subunit 2 (PolG2) encodes the accessory subunit of mitocondrial DNA polymerase gamma, which is responsible for the replication and repair of the mitochondrial genome.
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