PolG2

UniProt ID: Q9VJV8
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

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.

Existing Annotations Review

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

Core Functions

Accessory subunit of Pol gamma that increases the catalytic efficiency and processivity of the PolG1 catalytic subunit during mtDNA replication.

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:11917141
    Mutations in the accessory subunit cause lethality during early pupation, concomitant with loss of mtDNA and mitochondrial mass
  • file:DROME/PolG2/PolG2-deep-research-falcon.md
    PolG2 helps that catalytic subunit function efficiently during mitochondrial DNA (mtDNA) synthesis

References

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Suggested Questions for Experts

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?

Suggested Experiments

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.

Deep Research

Falcon

(PolG2-deep-research-falcon.md)

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FlyBase

(PolG2-deep-research-flybase.md)
FlyBase gene description for PolG2 (DROME) FlyBase

FlyBase gene description for PolG2 (DROME)

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.

πŸ“š Additional Documentation

Notes

(PolG2-notes.md)

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πŸ“„ View Raw YAML

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