DPOD3_DROME
ID DPOD3_DROME Reviewed; 431 AA.
AC Q9Y118;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=DNA polymerase delta subunit 3 {ECO:0000312|FlyBase:FBgn0283467};
DE AltName: Full=Pol32 polymerase delta subunit 3 {ECO:0000250|UniProtKB:P47110};
GN Name=PolD3 {ECO:0000312|FlyBase:FBgn0283467};
GN Synonyms=DNApolD3 {ECO:0000305}, Pol32 {ECO:0000250|UniProtKB:P47110},
GN rd {ECO:0000312|EMBL:AAF53445.1};
GN ORFNames=CG3975 {ECO:0000312|FlyBase:FBgn0283467};
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 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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 [2] {ECO:0000312|Proteomes:UP000000803}
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 [3] {ECO:0000312|EMBL:AAD38629.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA Harvey D.A.;
RT "A Drosophila complementary DNA resource.";
RL Science 287:2222-2224(2000).
RN [4] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF 15-ASP--LYS-431.
RX PubMed=22532806; DOI=10.1371/journal.pgen.1002659;
RA Kane D.P., Shusterman M., Rong Y., McVey M.;
RT "Competition between replicative and translesion polymerases during
RT homologous recombination repair in Drosophila.";
RL PLoS Genet. 8:E1002659-E1002659(2012).
RN [5] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25826374; DOI=10.1371/journal.pone.0120859;
RA Tritto P., Palumbo V., Micale L., Marzulli M., Bozzetti M.P., Specchia V.,
RA Palumbo G., Pimpinelli S., Berloco M.;
RT "Loss of Pol32 in Drosophila melanogaster causes chromosome instability and
RT suppresses variegation.";
RL PLoS ONE 10:E0120859-E0120859(2015).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=31053594; DOI=10.1534/genetics.119.302247;
RA Bhandari J., Karg T., Golic K.G.;
RT "Homolog-Dependent Repair Following Dicentric Chromosome Breakage in
RT Drosophila melanogaster.";
RL Genetics 212:615-630(2019).
RN [7] {ECO:0000305}
RP FUNCTION, IDENTIFICATION IN THE DNA POLYMERASE DELTA COMPLEX, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF 55-PHE--VAL-88; 64-GLN--ARG-80; 371-ASP--ASP-373;
RP 371-ASP--THR-378; 374-GLY--THR-378; 421-GLN--ILE-424 AND 421-GLN--PHE-428.
RX PubMed=31100062; DOI=10.1371/journal.pgen.1008169;
RA Ji J., Tang X., Hu W., Maggert K.A., Rong Y.S.;
RT "The processivity factor Pol32 mediates nuclear localization of DNA
RT polymerase delta and prevents chromosomal fragile site formation in
RT Drosophila development.";
RL PLoS Genet. 15:E1008169-E1008169(2019).
CC -!- FUNCTION: Accessory component of the DNA polymerase delta complex and
CC possibly the DNA polymerase zeta complex (By similarity). As a
CC component of the delta complex, participates in high fidelity genome
CC replication, including lagging strand synthesis, DNA recombination and
CC repair (PubMed:22532806, PubMed:25826374, PubMed:31100062). Required to
CC recruit the DNA polymerase delta complex to the nucleus of rapidly
CC dividing embryonic cells, and as a consequence is essential for genome
CC replication during the earliest cell cycles (PubMed:31100062,
CC PubMed:25826374). Increases the efficiency and processivity of DNA
CC synthesis of the DNA polymerases during mitotic DNA replication and
CC repair (PubMed:22532806, PubMed:25826374, PubMed:31100062). During
CC development this function is essential for preventing replication
CC stress that results in the formation of chromosomal fragile sites (CFS)
CC such as chromosomal breaks (PubMed:31100062, PubMed:25826374). Ensures
CC genomic stability by promoting several types of DNA repair mechanisms
CC including repairing broken dicentric chromosomes through homolog-
CC dependent break-induced replication (BIR) (PubMed:22532806,
CC PubMed:25826374, PubMed:31053594). During homologous recombination (HR)
CC repair, required for maintaining the processivity of the delta complex
CC during break-induced replication; a form of HR that requires extensive
CC DNA synthesis such as the repair of large gaps (PubMed:25826374,
CC PubMed:22532806). Able to suppress position effect variegation and may
CC therefore have a role in the induction of chromatin state changes that
CC likely include its activities in DNA replication and repair
CC (PubMed:25826374). {ECO:0000250|UniProtKB:Q15054,
CC ECO:0000269|PubMed:22532806, ECO:0000269|PubMed:25826374,
CC ECO:0000269|PubMed:31053594, ECO:0000269|PubMed:31100062}.
CC -!- SUBUNIT: Component of both the DNA polymerase delta and DNA polymerase
CC zeta complexes (By similarity). The DNA polymerase delta complex
CC consists of three subunits: the catalytic subunit PolD1 and two
CC accessory subunits PolD2/Pol31 and PolD3/Pol32 (PubMed:31100062).
CC Within the delta complex, interacts with both PolD1 and PolD2
CC (PubMed:31100062). Component of the DNA polymerase zeta complex
CC consisting of four subunits: the catalytic subunit PolZ1 and three
CC accessory subunits PolZ2/Rev7, PolD2/Pol31 and PolD3/Pol32 (By
CC similarity). {ECO:0000250|UniProtKB:P49005,
CC ECO:0000269|PubMed:31100062}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:31100062}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:31100062}. Note=During oogenesis,
CC detected in the nuclei of nurse cells, follicle cells, and in the
CC nucleoplasm of the oocyte. In syncytial cell cycles, accumulates in the
CC nucleus during interphase but disperses into the nucleoplasm at the
CC onset of mitosis. {ECO:0000269|PubMed:31100062}.
CC -!- TISSUE SPECIFICITY: Expressed in ovaries (at the protein level)
CC (PubMed:31100062). Expressed in ovaries (PubMed:25826374).
CC {ECO:0000269|PubMed:25826374, ECO:0000269|PubMed:31100062}.
CC -!- DEVELOPMENTAL STAGE: Expressed in adult females and embryos (at the
CC protein level). {ECO:0000269|PubMed:31100062}.
CC -!- DISRUPTION PHENOTYPE: Oocytes and embryos lacking maternal PolD3, show
CC no nuclear localization of the delta complex members PolD1 and PolD2,
CC resulting in limited genome replication during the earliest cell cycles
CC and thus early developmental arrest (PubMed:31100062). Mutants,
CC presumably with maternal but not zygotic PolD3, develop normally
CC however adults display a variable degree of bristle loss or shortening,
CC and females are sterile while males are fertile (PubMed:31100062). In
CC larval salivary glands, the delta complex localizes normally to the
CC nuclei and chromosomes display a significant decrease in homologous
CC recombination repair (PubMed:31100062). Chromosomes also exhibit
CC spontaneous double strand breaks that primarily result from defects in
CC genomic replication and, to a lesser extent, in DNA repair synthesis
CC (PubMed:31100062). {ECO:0000269|PubMed:31100062}.
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DR EMBL; AE014134; AAF53445.1; -; Genomic_DNA.
DR EMBL; AE014134; ADV37066.1; -; Genomic_DNA.
DR EMBL; FM245602; CAR93528.1; -; Genomic_DNA.
DR EMBL; FM245606; CAR93532.1; -; Genomic_DNA.
DR EMBL; FM245609; CAR93535.1; -; Genomic_DNA.
DR EMBL; AF145654; AAD38629.1; -; mRNA.
DR RefSeq; NP_001188816.1; NM_001201887.2.
DR RefSeq; NP_609743.1; NM_135899.3.
DR AlphaFoldDB; Q9Y118; -.
DR SMR; Q9Y118; -.
DR IntAct; Q9Y118; 6.
DR STRING; 7227.FBpp0292263; -.
DR PaxDb; Q9Y118; -.
DR PRIDE; Q9Y118; -.
DR DNASU; 34892; -.
DR EnsemblMetazoa; FBtr0303164; FBpp0292263; FBgn0283467.
DR EnsemblMetazoa; FBtr0336864; FBpp0307818; FBgn0283467.
DR GeneID; 34892; -.
DR KEGG; dme:Dmel_CG3975; -.
DR UCSC; CG3975-RA; d. melanogaster.
DR CTD; 34892; -.
DR FlyBase; FBgn0283467; PolD3.
DR VEuPathDB; VectorBase:FBgn0283467; -.
DR eggNOG; ENOG502QPSW; Eukaryota.
DR HOGENOM; CLU_666107_0_0_1; -.
DR InParanoid; Q9Y118; -.
DR OMA; FVITQRK; -.
DR OrthoDB; 1384221at2759; -.
DR PhylomeDB; Q9Y118; -.
DR SignaLink; Q9Y118; -.
DR BioGRID-ORCS; 34892; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 34892; -.
DR PRO; PR:Q9Y118; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0283467; Expressed in ovary and 12 other tissues.
DR ExpressionAtlas; Q9Y118; baseline and differential.
DR GO; GO:0043625; C:delta DNA polymerase complex; IDA:FlyBase.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0016035; C:zeta DNA polymerase complex; ISS:FlyBase.
DR GO; GO:0030337; F:DNA polymerase processivity factor activity; IMP:FlyBase.
DR GO; GO:0006281; P:DNA repair; IMP:FlyBase.
DR GO; GO:0043150; P:DNA synthesis involved in double-strand break repair via homologous recombination; IMP:FlyBase.
DR GO; GO:0000727; P:double-strand break repair via break-induced replication; IMP:FlyBase.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:FlyBase.
DR GO; GO:1902969; P:mitotic DNA replication; IMP:FlyBase.
DR GO; GO:1900264; P:positive regulation of DNA-directed DNA polymerase activity; IMP:FlyBase.
DR GO; GO:0031503; P:protein-containing complex localization; IMP:UniProtKB.
PE 1: Evidence at protein level;
KW DNA damage; DNA repair; DNA replication; Nucleus; Reference proteome.
FT CHAIN 1..431
FT /note="DNA polymerase delta subunit 3"
FT /id="PRO_0000448687"
FT REGION 64..80
FT /note="Necessary for function, possibly resulting from its
FT inability to interact with PolD2"
FT /evidence="ECO:0000269|PubMed:31100062"
FT REGION 128..431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 137..167
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 168..198
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 227..241
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 250..278
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 279..296
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 305..366
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 15..431
FT /note="Missing: Homologous recombination repair is reduced
FT by 70% resulting in mutants displaying extreme sensitivity
FT to various DNA damaging agents, except for camptothecin."
FT /evidence="ECO:0000269|PubMed:22532806"
FT MUTAGEN 55..88
FT /note="Missing: Unable to rescue bristle and female
FT fertility defects in mutants."
FT /evidence="ECO:0000269|PubMed:31100062"
FT MUTAGEN 64..80
FT /note="Missing: Unable to rescue bristle and female
FT fertility defects in mutants."
FT /evidence="ECO:0000269|PubMed:31100062"
FT MUTAGEN 371..378
FT /note="Missing: Rescues bristle and female fertility
FT defects in mutants."
FT /evidence="ECO:0000269|PubMed:31100062"
FT MUTAGEN 371..373
FT /note="DED->AAA: Rescues bristle and female fertility
FT defects in mutants."
FT /evidence="ECO:0000269|PubMed:31100062"
FT MUTAGEN 374..378
FT /note="GFVIT->AFVAA: Rescues bristle and female fertility
FT defects in mutants."
FT /evidence="ECO:0000269|PubMed:31100062"
FT MUTAGEN 421..428
FT /note="Missing: Rescues bristle and female fertility
FT defects in mutants."
FT /evidence="ECO:0000269|PubMed:31100062"
FT MUTAGEN 421..424
FT /note="QAGI->AAGA: Rescues bristle and female fertility
FT defects in mutants."
FT /evidence="ECO:0000269|PubMed:31100062"
SQ SEQUENCE 431 AA; 47046 MW; A8C8A0460E5CA7DC CRC64;
MSLKKALDDC MIDFDRCVLV TDLLEEYKLS YKEVNDVLEA YIKEQEPATK FEKRFLVHGK
RKTQGSDSGE DLYSVVLESR MQDWLAKVQD AESQLYSVKI AGGTKAPAAI FKPMQHLEVK
LAKVEQRPGA GKIVPSANGT TPHNGVKSEP TKSEPSKSAV KLEPSKSSLK SEPAKSKAEK
PVASKSSPED KKTSPKEQAS KAKPAAAKKG SINSFFTAAA SKPKDVKATP SKSTSGTVDN
FFKKQPAGAK KSPPESEDKS KKDASNSNKK EASKKKSPSP TKKPTTANTS MQLFDEESAE
SSDEEEKLDM LRRKVIESDN DSDQEKASSS KRRRISDSED EEQPPKKSAD EETIALDEKM
DTEPANETYL DEDGFVITQR KPTKAQPANK KVSPKAAAPV NKKKSPPSAA KAGKDAPKTK
QAGIMNFFSK K
