DPOG1_DROME
ID DPOG1_DROME Reviewed; 1145 AA.
AC Q27607; B5RIX0; Q8T4E6; Q94906; Q9V442;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JAN-2003, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=DNA polymerase subunit gamma-1, mitochondrial {ECO:0000305};
DE EC=2.7.7.7 {ECO:0000269|PubMed:15537632, ECO:0000269|PubMed:26554610, ECO:0000269|PubMed:2671990, ECO:0000269|PubMed:28430993, ECO:0000269|PubMed:3095323, ECO:0000269|PubMed:8798543};
DE AltName: Full=3'-5' exodeoxyribonuclease {ECO:0000305};
DE EC=3.1.11.- {ECO:0000269|PubMed:15537632, ECO:0000269|PubMed:26554610, ECO:0000269|PubMed:2671990, ECO:0000269|PubMed:28430993, ECO:0000269|PubMed:8798543};
DE AltName: Full=DNA polymerase gamma subunit 1 {ECO:0000312|FlyBase:FBgn0004406};
DE AltName: Full=Mitochondrial DNA polymerase catalytic subunit {ECO:0000305};
DE Short=Protein tamas {ECO:0000303|PubMed:11917141};
DE Flags: Precursor;
GN Name=PolG1 {ECO:0000312|FlyBase:FBgn0004406};
GN Synonyms=DNApol-gamma {ECO:0000312|FlyBase:FBgn0004406},
GN DNApol-gamma125 {ECO:0000312|FlyBase:FBgn0004406}, DNApolG1 {ECO:0000305},
GN l(2)34Dc {ECO:0000312|FlyBase:FBgn0004406},
GN l(2)br5 {ECO:0000312|FlyBase:FBgn0004406},
GN MtPolA {ECO:0000312|FlyBase:FBgn0004406},
GN pol gamma-alpha {ECO:0000303|PubMed:10930405,
GN ECO:0000312|FlyBase:FBgn0004406}, Polg {ECO:0000312|FlyBase:FBgn0004406},
GN tam {ECO:0000303|PubMed:11917141};
GN ORFNames=CG8987 {ECO:0000312|FlyBase:FBgn0004406};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8884268; DOI=10.1006/geno.1996.0490;
RA Ropp P.A., Copeland W.C.;
RT "Cloning and characterization of the human mitochondrial DNA polymerase,
RT DNA polymerase gamma.";
RL Genomics 36:449-458(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RC TISSUE=Ovary;
RX PubMed=8798543; DOI=10.1074/jbc.271.38.23389;
RA Lewis D.L., Farr C.L., Wang Y., Lagina A.T. III, Kaguni L.S.;
RT "Catalytic subunit of mitochondrial DNA polymerase from Drosophila embryos.
RT Cloning, bacterial overexpression, and biochemical characterization.";
RL J. Biol. Chem. 271:23389-23394(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10471707; DOI=10.1093/genetics/153.1.179;
RA Ashburner M., Misra S., Roote J., Lewis S.E., Blazej R.G., Davis T.,
RA Doyle C., Galle R.F., George R.A., Harris N.L., Hartzell G., Harvey D.A.,
RA Hong L., Houston K.A., Hoskins R.A., Johnson G., Martin C., Moshrefi A.R.,
RA Palazzolo M., Reese M.G., Spradling A.C., Tsang G., Wan K.H., Whitelaw K.,
RA Celniker S.E., Rubin G.M.;
RT "An exploration of the sequence of a 2.9-Mb region of the genome of
RT Drosophila melanogaster: the Adh region.";
RL Genetics 153:179-219(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [5]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Testis;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Carlson J.W., Booth B., Frise E., Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, IDENTIFICATION IN THE DNA POLYMERASE GAMMA
RP COMPLEX, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=3095323; DOI=10.1016/s0021-9258(18)66938-8;
RA Wernette C.M., Kaguni L.S.;
RT "A mitochondrial DNA polymerase from embryos of Drosophila melanogaster.
RT Purification, subunit structure, and partial characterization.";
RL J. Biol. Chem. 261:14764-14770(1986).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=2671990; DOI=10.1073/pnas.86.17.6469;
RA Kaguni L.S., Olson M.W.;
RT "Mismatch-specific 3'----5' exonuclease associated with the mitochondrial
RT DNA polymerase from Drosophila embryos.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:6469-6473(1989).
RN [10]
RP FUNCTION, AND IDENTIFICATION IN THE DNA POLYMERASE GAMMA COMPLEX.
RX PubMed=7499423; DOI=10.1074/jbc.270.48.28932;
RA Olson M.W., Wang Y., Elder R.H., Kaguni L.S.;
RT "Subunit structure of mitochondrial DNA polymerase from Drosophila embryos.
RT Physical and immunological studies.";
RL J. Biol. Chem. 270:28932-28937(1995).
RN [11]
RP IDENTIFICATION IN THE DNA POLYMERASE GAMMA COMPLEX.
RX PubMed=9153213; DOI=10.1074/jbc.272.21.13640;
RA Wang Y., Farr C.L., Kaguni L.S.;
RT "Accessory subunit of mitochondrial DNA polymerase from Drosophila embryos.
RT Cloning, molecular analysis, and association in the native enzyme.";
RL J. Biol. Chem. 272:13640-13646(1997).
RN [12]
RP DEVELOPMENTAL STAGE.
RX PubMed=10930405; DOI=10.1074/jbc.m003024200;
RA Lefai E., Fernandez-Moreno M.A., Alahari A., Kaguni L.S., Garesse R.;
RT "Differential regulation of the catalytic and accessory subunit genes of
RT Drosophila mitochondrial DNA polymerase.";
RL J. Biol. Chem. 275:33123-33133(2000).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF GLU-595.
RX PubMed=11917141; DOI=10.1073/pnas.072664899;
RA Iyengar B., Luo N., Farr C.L., Kaguni L.S., Campos A.R.;
RT "The accessory subunit of DNA polymerase gamma is essential for
RT mitochondrial DNA maintenance and development in Drosophila melanogaster.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:4483-4488(2002).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 413-ARG--ARG-470;
RP 419-TYR--ASP-421; 483-ASN--ILE-533; 536-ASP--ILE-581; 556-PRO--LEU-558;
RP TRP-576; 666-CYS--PRO-742; 687-LYS--PHE-689 AND 719-SER--TRP-721.
RX PubMed=15537632; DOI=10.1074/jbc.m411447200;
RA Luo N., Kaguni L.S.;
RT "Mutations in the spacer region of Drosophila mitochondrial DNA polymerase
RT affect DNA binding, processivity, and the balance between Pol and Exo
RT function.";
RL J. Biol. Chem. 280:2491-2497(2005).
RN [15]
RP FUNCTION, AND MUTAGENESIS OF GLU-595 AND 1085-SER--SER-1145.
RX PubMed=19924234; DOI=10.1371/journal.pone.0007874;
RA Baqri R.M., Turner B.A., Rheuben M.B., Hammond B.D., Kaguni L.S.,
RA Miller K.E.;
RT "Disruption of mitochondrial DNA replication in Drosophila increases
RT mitochondrial fast axonal transport in vivo.";
RL PLoS ONE 4:E7874-E7874(2009).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ASP-263; GLN-1009 AND HIS-1038.
RX PubMed=26554610; DOI=10.1038/ncomms9808;
RA Bratic A., Kauppila T.E., Macao B., Groenke S., Siibak T., Stewart J.B.,
RA Baggio F., Dols J., Partridge L., Falkenberg M., Wredenberg A.,
RA Larsson N.G.;
RT "Complementation between polymerase- and exonuclease-deficient
RT mitochondrial DNA polymerase mutants in genomically engineered flies.";
RL Nat. Commun. 6:8808-8808(2015).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ASP-263 AND GLU-813.
RX PubMed=28318978; DOI=10.1016/j.cub.2017.02.014;
RA Yu Z., O'Farrell P.H., Yakubovich N., DeLuca S.Z.;
RT "The mitochondrial DNA polymerase promotes elimination of paternal
RT mitochondrial genomes.";
RL Curr. Biol. 27:1033-1039(2017).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-873.
RX PubMed=28430993; DOI=10.1093/hmg/ddx146;
RA Siibak T., Clemente P., Bratic A., Bruhn H., Kauppila T.E.S., Macao B.,
RA Schober F.A., Lesko N., Wibom R., Naess K., Nennesmo I., Wedell A.,
RA Peter B., Freyer C., Falkenberg M., Wredenberg A.;
RT "A multi-systemic mitochondrial disorder due to a dominant p.Y955H disease
RT variant in DNA polymerase gamma.";
RL Hum. Mol. Genet. 26:2515-2525(2017).
CC -!- FUNCTION: As the catalytic component of the DNA polymerase gamma
CC complex is involved in the replication of mitochondrial DNA (mtDNA)
CC (PubMed:3095323, PubMed:7499423, PubMed:8798543, PubMed:11917141,
CC PubMed:19924234, PubMed:15537632, PubMed:28430993). Has both 5'-3' DNA
CC polymerase and a highly mispair-specific 3'-5' exonuclease activity
CC (PubMed:2671990, PubMed:7499423, PubMed:8798543, PubMed:28430993,
CC PubMed:26554610, PubMed:15537632). At the end of mtDNA replication DNA
CC ends are ligated to produce a closed circular mtDNA molecule, its
CC exonuclease activity is required for formation of these ligatable ends
CC by preventing DNA synthesis from continuing past the 5'-end of
CC downstream DNA into duplex DNA regions (PubMed:28430993). Does not
CC possess DNA primase activity, does not catalyze strand displacement
CC synthesis and does not contain a 5'-3' exonuclease activity to catalyze
CC nick translation (PubMed:3095323). Important for promoting the
CC elimination of paternal mitochondrial DNA during spermatogenesis,
CC however its exact role in this function has not yet been identified and
CC appears to be independent of its 3'-5'-exonuclease activity and only
CC partially dependent on its DNA polymerase activity (PubMed:28318978).
CC {ECO:0000269|PubMed:11917141, ECO:0000269|PubMed:15537632,
CC ECO:0000269|PubMed:19924234, ECO:0000269|PubMed:26554610,
CC ECO:0000269|PubMed:2671990, ECO:0000269|PubMed:28318978,
CC ECO:0000269|PubMed:28430993, ECO:0000269|PubMed:3095323,
CC ECO:0000269|PubMed:7499423, ECO:0000269|PubMed:8798543}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.7;
CC Evidence={ECO:0000269|PubMed:15537632, ECO:0000269|PubMed:26554610,
CC ECO:0000269|PubMed:2671990, ECO:0000269|PubMed:28430993,
CC ECO:0000269|PubMed:3095323, ECO:0000269|PubMed:8798543};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22509;
CC Evidence={ECO:0000269|PubMed:2671990};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22510;
CC Evidence={ECO:0000269|PubMed:2671990};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:3095323};
CC -!- ACTIVITY REGULATION: Stimulated by KCl, and inhibited by the small
CC molecules o 2',3'-dideoxythymidine 5'-triphosphate (d2TTP) and N-
CC ethylmaleimide (NEM). {ECO:0000269|PubMed:3095323}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.97 uM for deoxythymidine triphosphate
CC {ECO:0000269|PubMed:3095323};
CC pH dependence:
CC Optimum pH is 9.0. {ECO:0000269|PubMed:3095323};
CC -!- SUBUNIT: Component of the DNA polymerase gamma complex consisting of
CC two subunits: the catalytic subunit DNApol-gamma/DNApolG1 and the
CC accessory subunit PolG2/DNApol-gamma35. {ECO:0000269|PubMed:3095323,
CC ECO:0000269|PubMed:7499423, ECO:0000269|PubMed:9153213}.
CC -!- INTERACTION:
CC Q27607; Q9VJV8: DNApol-gamma35; NbExp=2; IntAct=EBI-122256, EBI-852898;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:28318978,
CC ECO:0000269|PubMed:3095323}. Note=In sperm, detected in puncta that
CC associate with mitochondrial nucleoids at developmental stages when the
CC nucleoids are being eliminated. {ECO:0000269|PubMed:28318978}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the embryo (at protein levels)
CC (PubMed:3095323). Expressed at high levels in eggs and to a lesser
CC extent during embryonic development (PubMed:10930405). Expressed at all
CC larval stages and at higher levels in adults (PubMed:10930405).
CC {ECO:0000269|PubMed:10930405, ECO:0000269|PubMed:3095323}.
CC -!- DISRUPTION PHENOTYPE: Larval lethal due to severe defects in
CC mitochondrial DNA (mtDNA) replication and synthesis (PubMed:26554610).
CC Larvae display a severe decrease in body weight and a 70% decrease in
CC mtDNA levels but are able to survive on maternal contribution until the
CC third larval stage (PubMed:26554610). RNAi-mediated knockdown in male
CC germline cells, results in defective clearance of paternal
CC mitochondrial nucleoids (containing mitochondrial DNA) during
CC spermatogenesis (PubMed:28318978). Eggs fertilized by mutant males do
CC not display an increase in male mtDNA levels, suggesting that it does
CC not affect regulatory pathways in the embryo that prevent the paternal
CC transmission of mtDNA (PubMed:28318978). {ECO:0000269|PubMed:26554610,
CC ECO:0000269|PubMed:28318978}.
CC -!- SIMILARITY: Belongs to the DNA polymerase type-A family. {ECO:0000305}.
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DR EMBL; U60298; AAC47290.1; -; Genomic_DNA.
DR EMBL; U62547; AAC47658.1; -; mRNA.
DR EMBL; AE014134; AAF53338.1; -; Genomic_DNA.
DR EMBL; AY089226; AAL89964.1; -; mRNA.
DR EMBL; BT044244; ACH92309.1; -; mRNA.
DR PIR; T13808; T13808.
DR PIR; T13810; T13810.
DR RefSeq; NP_476821.1; NM_057473.4.
DR AlphaFoldDB; Q27607; -.
DR SMR; Q27607; -.
DR BioGRID; 60825; 5.
DR ComplexPortal; CPX-2096; Mitochondrial DNA polymerase gamma complex.
DR IntAct; Q27607; 2.
DR STRING; 7227.FBpp0080148; -.
DR PaxDb; Q27607; -.
DR PRIDE; Q27607; -.
DR EnsemblMetazoa; FBtr0080571; FBpp0080148; FBgn0004406.
DR GeneID; 34792; -.
DR KEGG; dme:Dmel_CG8987; -.
DR CTD; 8205; -.
DR FlyBase; FBgn0004406; PolG1.
DR VEuPathDB; VectorBase:FBgn0004406; -.
DR eggNOG; KOG3657; Eukaryota.
DR GeneTree; ENSGT00390000000453; -.
DR HOGENOM; CLU_001524_2_2_1; -.
DR InParanoid; Q27607; -.
DR OMA; LWLWDED; -.
DR OrthoDB; 86850at2759; -.
DR PhylomeDB; Q27607; -.
DR BioGRID-ORCS; 34792; 0 hits in 1 CRISPR screen.
DR ChiTaRS; pyd; fly.
DR GenomeRNAi; 34792; -.
DR PRO; PR:Q27607; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0004406; Expressed in egg cell and 16 other tissues.
DR Genevisible; Q27607; DM.
DR GO; GO:0005760; C:gamma DNA polymerase complex; IDA:FlyBase.
DR GO; GO:0005759; C:mitochondrial matrix; IC:ComplexPortal.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase.
DR GO; GO:0008408; F:3'-5' exonuclease activity; IBA:GO_Central.
DR GO; GO:0008296; F:3'-5'-exodeoxyribonuclease activity; IDA:FlyBase.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IDA:FlyBase.
DR GO; GO:0000166; F:nucleotide binding; IDA:UniProtKB.
DR GO; GO:0045004; P:DNA replication proofreading; IDA:FlyBase.
DR GO; GO:0006261; P:DNA-templated DNA replication; IDA:FlyBase.
DR GO; GO:0006264; P:mitochondrial DNA replication; IMP:FlyBase.
DR GO; GO:0000001; P:mitochondrion inheritance; IMP:UniProtKB.
DR GO; GO:0030382; P:sperm mitochondrion organization; IMP:UniProtKB.
DR InterPro; IPR019760; DNA-dir_DNA_pol_A_CS.
DR InterPro; IPR002297; DNA-dir_DNA_pol_A_mt.
DR InterPro; IPR001098; DNA-dir_DNA_pol_A_palm_dom.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR041336; DNApol_Exo.
DR InterPro; IPR012337; RNaseH-like_sf.
DR PANTHER; PTHR10267; PTHR10267; 1.
DR Pfam; PF00476; DNA_pol_A; 1.
DR Pfam; PF18136; DNApol_Exo; 1.
DR PRINTS; PR00867; DNAPOLG.
DR SMART; SM00482; POLAc; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS00447; DNA_POLYMERASE_A; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; DNA replication; DNA-binding;
KW DNA-directed DNA polymerase; Hydrolase; Magnesium; Mitochondrion;
KW Nucleotidyltransferase; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..9
FT /note="Mitochondrion"
FT CHAIN 10..1145
FT /note="DNA polymerase subunit gamma-1, mitochondrial"
FT /id="PRO_0000007313"
FT MUTAGEN 263
FT /note="D->A: Defects in mitochondrial DNA (mtDNA)
FT replication and synthesis results in pupal lethality. Only
FT half of the mutants survive to the pupal stage but die
FT shortly afterwards. Larvae display an accumulation of point
FT mutations and linear deletions of mtDNA. No decrease in
FT larvae body weight. Unable to rescue the defective
FT clearance of paternal mitochondrial nucleoids in mutants."
FT /evidence="ECO:0000269|PubMed:26554610,
FT ECO:0000269|PubMed:28318978"
FT MUTAGEN 413..470
FT /note="Missing: Greatly reduces polymerase activity."
FT /evidence="ECO:0000269|PubMed:15537632"
FT MUTAGEN 419..421
FT /note="YED->AAA: In YED; slight reduction in polymerase
FT activity."
FT /evidence="ECO:0000269|PubMed:15537632"
FT MUTAGEN 483..533
FT /note="Missing: Slight reduction in polymerase activity."
FT /evidence="ECO:0000269|PubMed:15537632"
FT MUTAGEN 536..581
FT /note="Missing: Greatly reduces polymerase activity."
FT /evidence="ECO:0000269|PubMed:15537632"
FT MUTAGEN 556..558
FT /note="PKL->AAA: In PKL; severe reduction in polymerase
FT activity."
FT /evidence="ECO:0000269|PubMed:15537632"
FT MUTAGEN 576
FT /note="W->A: Severe reduction in polymerase activity."
FT /evidence="ECO:0000269|PubMed:15537632"
FT MUTAGEN 595
FT /note="E->A: Loss of mitochondrial DNA which disrupts
FT mitochondrial morphology; larval brains are smaller due to
FT defective cell proliferation leading to death at the pupal
FT stage. Leads to higher mitochondrial density in proximal
FT nerves and muscles as well as increased flux of
FT bidirectional mitochondrial axonal transport; when
FT associated with 1085-S--S-1145 DEL."
FT /evidence="ECO:0000269|PubMed:11917141,
FT ECO:0000269|PubMed:19924234"
FT MUTAGEN 666..742
FT /note="Missing: Greatly reduces polymerase activity."
FT /evidence="ECO:0000269|PubMed:15537632"
FT MUTAGEN 687..689
FT /note="KDF->AAA: In KDF; reduction in polymerase activity."
FT /evidence="ECO:0000269|PubMed:15537632"
FT MUTAGEN 719..721
FT /note="SYW->AAA: In SYW; severe reduction in polymerase
FT activity."
FT /evidence="ECO:0000269|PubMed:15537632"
FT MUTAGEN 813
FT /note="E->V: Partially rescues the defective clearance of
FT paternal mitochondrial nucleoids in mutants."
FT /evidence="ECO:0000269|PubMed:28318978"
FT MUTAGEN 873
FT /note="Y->C: Defects in mitochondrial DNA (mtDNA)
FT replication and synthesis results in larval lethality at
FT the third instar stage. Displays increased exonuclease
FT activity and shows replicative stalling, particularly at
FT dATP insertion sites. Defective replication and synthesis
FT results in decreased levels of mtDNA but does not result in
FT multiple linear deletions in mtDNA. No effect on DNA
FT binding."
FT /evidence="ECO:0000269|PubMed:28430993"
FT MUTAGEN 873
FT /note="Y->H: Severe defects in mitochondrial DNA (mtDNA)
FT replication and synthesis results in larval lethality at
FT the third instar stage. Exonuclease activity is increased,
FT and displays replicative stalling, particularly at dATP
FT insertion sites, and decreased DNA binding. Defective
FT replication and synthesis results in decreased levels of
FT mtDNA but does not result in multiple linear deletions in
FT mtDNA."
FT /evidence="ECO:0000269|PubMed:28430993"
FT MUTAGEN 1009
FT /note="Q->A: Defects in mitochondrial DNA (mtDNA)
FT replication and synthesis results in the death of most
FT mutants at the third instar stage. Only two percent survive
FT to the pupal stage but die shortly afterwards. Five day old
FT larvae display a severe decrease in mtDNA levels and a
FT significant reduction in body weight."
FT /evidence="ECO:0000269|PubMed:26554610"
FT MUTAGEN 1038
FT /note="H->A: Defects in mitochondrial DNA (mtDNA)
FT replication and synthesis results in larval lethality at
FT the third instar stage. Larvae 5 days old, display a severe
FT decrease in mtDNA levels and a significant reduction in
FT body weight. Does not result in linear deletions of mtDNA."
FT /evidence="ECO:0000269|PubMed:26554610"
FT MUTAGEN 1085..1145
FT /note="Missing: Loss of mitochondrial DNA which disrupts
FT mitochondrial morphology, leads to higher mitochondrial
FT density in proximal nerves and muscles as well as increased
FT flux of bidirectional mitochondrial axonal transport; when
FT associated with Ala-595."
FT /evidence="ECO:0000269|PubMed:19924234"
FT CONFLICT 114
FT /note="A -> P (in Ref. 2; AAC47658)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="T -> P (in Ref. 2; AAC47658)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="T -> S (in Ref. 2; AAC47658)"
FT /evidence="ECO:0000305"
FT CONFLICT 273
FT /note="T -> I (in Ref. 2; AAC47658)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="S -> P (in Ref. 2; AAC47658)"
FT /evidence="ECO:0000305"
FT CONFLICT 326
FT /note="V -> L (in Ref. 1; AAC47290)"
FT /evidence="ECO:0000305"
FT CONFLICT 478
FT /note="L -> I (in Ref. 2; AAC47658)"
FT /evidence="ECO:0000305"
FT CONFLICT 530
FT /note="A -> E (in Ref. 2; AAC47658)"
FT /evidence="ECO:0000305"
FT CONFLICT 600
FT /note="H -> R (in Ref. 2; AAC47658)"
FT /evidence="ECO:0000305"
FT CONFLICT 732
FT /note="M -> L (in Ref. 2; AAC47658)"
FT /evidence="ECO:0000305"
FT CONFLICT 952
FT /note="N -> K (in Ref. 1; AAC47290 and 6; AAL89964)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1145 AA; 129828 MW; 186AD02B63827707 CRC64;
MQFHLIRKYA SKVSREHYAS SSVKIFRRVK PPQKVNKPKK PENVENGPTE YAENLVKVQM
ISRNLHAQLF PQAPRSISEQ QVASAKVYKD ELRRHGVDIE SSAPVSDVQL KLPALRGANI
EEHFHNIAKE QVQPYEELLL PLVQCEQLPK RPKRWAFHTG WTAYDPEDGT ATPVDHPLEK
GLVFDVEVCV SEGQAPVLAT AVSTKRWYSW VSSKLTKHRL SVEKLEPLDV DTDSERPHYT
TDELIPLGTT GPGLVVGHNV SYDRARLKEQ YLTEDTGTRF VDTMSLHMCV SGVTSYQRAM
LKSKKEPAAE DLGWLEQSSL NSLVEVHRLY CGGDTLSKEP RNIFVEGTLE QVRQSFQSLT
NYCASDVEAT HRILRVLYPL YAERFPHPAS LAGMLEMGSA YLPVNSNWER YIREAQLTYE
DLSIEAKYHL GRRAEEACSL LLDDQYRQNL WLWDEDWSVQ ELKLKQPPKR KPLPTVELKD
SGNTPEERRL QAKFQHLYDQ QALLPARRPL LPGYPLWYRK LCRKPPAKRA DEILEDDEEP
WSPGASEIST GMQIAPKLLS LCWEGYPLHY EREQGWGFLV PFRSDSEGVD RLPMEQLLAH
CPVPEFARLS ASKAESDMAF DMLPGQVEQH LGKREHYKKL SQKQQRLETQ YQGSGVWCNK
VLDDCCFFLK LPHKNGPSFR VGNPLSKDFL NKFAENVLSS GDPSCQAAAR VIDIARMMSY
WRNNRDRIMG QMVVWLDSQQ LPNEFTGEKC QPIAYGAICP QVVACGTLTR RAMEPTWMTA
SNSRPDRLGS ELRSMVQAPP GYRLVGADVD SQELWIASVL GDAYACGEHG ATPLGWMTLS
GSKSNGSDMH SITAKAVGIS RDHAKVINYA RIYGAGQLFA ETLLRQFNPT FSASEAKAKA
MKMFSITKGK RVYRLREEFH DELEDRAYSS YEASRLAIQR NRTLAEVFHR PNWQGGTESA
MFNRLEEIAT GSQPRTPFLG GRLSRALEAD TGPEQEQRFL PTRINWVVQS GAVDFLHLML
VSMRWLMGSH VRFCLSFHDE LRYLVKEELS PKAALAMHIT NLMTRSFCVS RIGLQDLPMS
VAFFSSVEVD TVLRKECTMD CKTPSNPHGL RIGYGIQPGQ SLSVAEAIEK AGGNDVSQWD
WIKKS
