DPOD1_BOVIN
ID DPOD1_BOVIN Reviewed; 1106 AA.
AC P28339;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=DNA polymerase delta catalytic subunit {ECO:0000305};
DE EC=2.7.7.7 {ECO:0000250|UniProtKB:P28340};
DE AltName: Full=3'-5' exodeoxyribonuclease {ECO:0000305};
DE EC=3.1.11.- {ECO:0000250|UniProtKB:P28340};
GN Name=POLD1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1721537; DOI=10.1021/bi00115a002;
RA Zhang J., Chung D.W., Tan C.-K., Downey K.M., Davie E.W., So A.G.;
RT "Primary structure of the catalytic subunit of calf thymus DNA polymerase
RT delta: sequence similarities with other DNA polymerases.";
RL Biochemistry 30:11742-11750(1991).
RN [2]
RP PROTEIN SEQUENCE OF 910-930 AND 968-977, IDENTIFICATION IN POL-DELTA
RP COMPLEX, AND MASS SPECTROMETRY.
RC TISSUE=Thymus;
RX PubMed=10751307; DOI=10.1074/jbc.m001217200;
RA Liu L., Mo J.-Y., Rodriguez-Belmonte E.M., Lee M.Y.W.T.;
RT "Identification of a fourth subunit of mammalian DNA polymerase delta.";
RL J. Biol. Chem. 275:18739-18744(2000).
RN [3]
RP ACTIVITY REGULATION BY KCTD13.
RX PubMed=11593007; DOI=10.1073/pnas.221452098;
RA He H., Tan C.-K., Downey K.M., So A.G.;
RT "A tumor necrosis factor alpha- and interleukin 6-inducible protein that
RT interacts with the small subunit of DNA polymerase delta and proliferating
RT cell nuclear antigen.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:11979-11984(2001).
RN [4]
RP INTERACTION WITH POLDIP2.
RX PubMed=12522211; DOI=10.1074/jbc.m208694200;
RA Liu L., Rodriguez-Belmonte E.M., Mazloum N., Xie B., Lee M.Y.W.T.;
RT "Identification of a novel protein, PDIP38, that interacts with the p50
RT subunit of DNA polymerase delta and proliferating cell nuclear antigen.";
RL J. Biol. Chem. 278:10041-10047(2003).
CC -!- FUNCTION: As the catalytic component of the trimeric (Pol-delta3
CC complex) and tetrameric DNA polymerase delta complexes (Pol-delta4
CC complex), plays a crucial role in high fidelity genome replication,
CC including in lagging strand synthesis, and repair. Exhibits both DNA
CC polymerase and 3'- to 5'-exonuclease activities. Requires the presence
CC of accessory proteins POLD2, POLD3 and POLD4 for full activity.
CC Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-
CC delta4), displays differences in catalytic activity. Most notably,
CC expresses higher proofreading activity in the context of Pol-delta3
CC compared with that of Pol-delta4. Although both Pol-delta3 and Pol-
CC delta4 process Okazaki fragments in vitro, Pol-delta3 may be better
CC suited to fulfill this task, exhibiting near-absence of strand
CC displacement activity compared to Pol-delta4 and stalling on encounter
CC with the 5'-blocking oligonucleotides. Pol-delta3 idling process may
CC avoid the formation of a gap, while maintaining a nick that can be
CC readily ligated. Along with DNA polymerase kappa, DNA polymerase delta
CC carries out approximately half of nucleotide excision repair (NER)
CC synthesis following UV irradiation. Under conditions of DNA replication
CC stress, in the presence of POLD3 and POLD4, may catalyze the repair of
CC broken replication forks through break-induced replication (BIR).
CC Involved in the translesion synthesis (TLS) of templates carrying O6-
CC methylguanine, 8oxoG or abasic sites. {ECO:0000250|UniProtKB:P28340}.
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:0000250|UniProtKB:P28340};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250};
CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Regulated by alteration of quaternary structure.
CC Exhibits burst rates of DNA synthesis are about 5 times faster in the
CC presence of POLD4 (Pol-delta4 complex) than in its absence (Pol-delta3
CC complex), while the affinity of the enzyme for its DNA and dNTP
CC substrates appears unchanged. The Pol-delta3 complex is more likely to
CC proofread DNA synthesis because it cleaves single-stranded DNA twice as
CC fast and transfers mismatched DNA from the polymerase to the
CC exonuclease sites 9 times faster compared to the Pol-delta3 complex.
CC Pol-delta3 also extends mismatched primers 3 times more slowly in the
CC absence of POLD4. The conversion of Pol-delta4 into Pol-delta3 is
CC induced by genotoxic stress or by replication stress leading POLD4
CC degradation (By similarity). Stimulated in the presence of PCNA (By
CC similarity). This stimulation is further increased in the presence of
CC KCTD13/PDIP1, most probably via direct interaction between KCTD13 and
CC POLD2 (PubMed:11593007). {ECO:0000250|UniProtKB:P28340,
CC ECO:0000269|PubMed:11593007}.
CC -!- SUBUNIT: Component of the tetrameric DNA polymerase delta complex (Pol-
CC delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and
CC POLD4/p12, with POLD1 bearing both DNA polymerase and 3' to 5'
CC proofreading exonuclease activities (PubMed:10751307). Within Pol-
CC delta4, directly interacts with POLD2 and POLD4. Following genotoxic
CC stress by DNA-damaging agents, such as ultraviolet light and methyl
CC methanesulfonate, or by replication stress induced by treatment with
CC hydroxyurea or aphidicolin, Pol-delta4 is converted into a trimeric
CC form of the complex (Pol-delta3) by POLD4 degradation. Pol-delta3 is
CC the major form at S phase replication sites and DNA damage sites. POLD1
CC displays different catalytic properties depending upon the complex it
CC is found in. It exhibits higher proofreading activity and fidelity than
CC Pol-delta4, making it particularly well suited to respond to DNA
CC damage. Directly interacts with PCNA, as do POLD3 and POLD4; this
CC interaction stimulates Pol-delta4 polymerase activity. As POLD2 and
CC POLD4, directly interacts with WRNIP1; this interaction stimulates DNA
CC polymerase delta-mediated DNA synthesis, independently of the presence
CC of PCNA. This stimulation may be due predominantly to an increase of
CC initiation frequency and also to increased processivity. Also observed
CC as a dimeric complex with POLD2 (Pol-delta2). Pol-delta2 is relatively
CC insensitive to the PCNA stimulation (2-5-fold) compared to Pol-delta4
CC that is stimulated by over 50-fold (By similarity). Interacts with
CC POLDIP2; this interaction is indirect and most probably mediated
CC through POLD2-binding (PubMed:12522211, PubMed:10751307) (By
CC similarity). Interacts with CIAO1 (By similarity). Interacts with
CC POLDIP2 (By similarity). {ECO:0000250|UniProtKB:P28340,
CC ECO:0000269|PubMed:10751307, ECO:0000269|PubMed:12522211}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P28340}.
CC Note=Colocalizes with PCNA and POLD3 at S phase replication sites.
CC After UV irradiation, recruited to DNA damage sites within 2 hours,
CC independently on the cell cycle phase, nor on PCNA ubiquitination. This
CC recruitment requires POLD3, PCNA and RFC1-replication factor C complex.
CC {ECO:0000250|UniProtKB:P28340}.
CC -!- DOMAIN: The CysB motif binds 1 4Fe-4S cluster and is required for the
CC formation of polymerase complexes. {ECO:0000250}.
CC -!- MISCELLANEOUS: In eukaryotes there are five DNA polymerases: alpha,
CC beta, gamma, delta, and epsilon which are responsible for different
CC reactions of DNA synthesis.
CC -!- SIMILARITY: Belongs to the DNA polymerase type-B family. {ECO:0000305}.
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DR EMBL; M80395; AAA30493.1; -; mRNA.
DR PIR; A39299; A39299.
DR RefSeq; NP_776852.1; NM_174427.2.
DR AlphaFoldDB; P28339; -.
DR SMR; P28339; -.
DR CORUM; P28339; -.
DR IntAct; P28339; 4.
DR STRING; 9913.ENSBTAP00000014714; -.
DR PaxDb; P28339; -.
DR PRIDE; P28339; -.
DR GeneID; 281990; -.
DR KEGG; bta:281990; -.
DR CTD; 5424; -.
DR eggNOG; KOG0969; Eukaryota.
DR InParanoid; P28339; -.
DR OrthoDB; 20210at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0043625; C:delta DNA polymerase complex; IDA:UniProtKB.
DR GO; GO:0008296; F:3'-5'-exodeoxyribonuclease activity; IBA:GO_Central.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; ISS:UniProtKB.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0006287; P:base-excision repair, gap-filling; IBA:GO_Central.
DR GO; GO:0034644; P:cellular response to UV; ISS:UniProtKB.
DR GO; GO:0071897; P:DNA biosynthetic process; IDA:UniProtKB.
DR GO; GO:0045004; P:DNA replication proofreading; IBA:GO_Central.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; ISS:UniProtKB.
DR GO; GO:0006261; P:DNA-templated DNA replication; IBA:GO_Central.
DR GO; GO:0070987; P:error-free translesion synthesis; ISS:UniProtKB.
DR GO; GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB.
DR GO; GO:0006297; P:nucleotide-excision repair, DNA gap filling; IBA:GO_Central.
DR Gene3D; 1.10.132.60; -; 1.
DR Gene3D; 3.30.420.10; -; 1.
DR Gene3D; 3.90.1600.10; -; 1.
DR InterPro; IPR006172; DNA-dir_DNA_pol_B.
DR InterPro; IPR017964; DNA-dir_DNA_pol_B_CS.
DR InterPro; IPR006133; DNA-dir_DNA_pol_B_exonuc.
DR InterPro; IPR006134; DNA-dir_DNA_pol_B_multi_dom.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR042087; DNA_pol_B_thumb.
DR InterPro; IPR023211; DNA_pol_palm_dom_sf.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR InterPro; IPR025687; Znf-C4pol.
DR Pfam; PF00136; DNA_pol_B; 1.
DR Pfam; PF03104; DNA_pol_B_exo1; 1.
DR Pfam; PF14260; zf-C4pol; 1.
DR PRINTS; PR00106; DNAPOLB.
DR SMART; SM00486; POLBc; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS00116; DNA_POLYMERASE_B; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Direct protein sequencing; DNA damage; DNA excision; DNA repair;
KW DNA replication; DNA-binding; DNA-directed DNA polymerase; Exonuclease;
KW Hydrolase; Iron; Iron-sulfur; Isopeptide bond; Metal-binding; Methylation;
KW Nuclease; Nucleotidyltransferase; Nucleus; Reference proteome; Transferase;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1106
FT /note="DNA polymerase delta catalytic subunit"
FT /id="PRO_0000046441"
FT ZN_FING 1011..1028
FT /note="CysA-type"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 4..19
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 1057..1075
FT /note="CysB motif"
FT BINDING 1011
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1014
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1025
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1028
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1057
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 1060
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 1070
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 1075
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT MOD_RES 19
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P28340"
FT CROSSLNK 573
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P28340"
SQ SEQUENCE 1106 AA; 123709 MW; EFC2ED155B290431 CRC64;
MDGKRRPGPG PGVPPKRARG GLWDEDEAYR PSQFEEELAL MEEMEAERRL QEQEEEELQS
ALEAADGQFS PTAIDARWLR PAPPALDPQM EPLIFQQLEI DHYVAPARPL PGAPPPSQDS
VPILRAFGVT NEGVSVCCHI HGFAPYFYTP APPGFGPEHL SELQRELSAA ISRDQRGGKE
LTGPAVLAVE LCSRESMFGY HGHGPSPFLR ITLALPRLMA PARRLLEQGI RLAGLGTPSF
APYEANVDFE IRFMVDTDIV GCNWLELPAG KYILRPEGKA TLCQLEADVL WSDVISHPPE
GEWQRIAPLR VLSFDIECAG RKGIFPEPER DPVIQICSLG LRWGEPEPFL RLALTLRPCA
PILGAKVQSY EREEDLLQAW STFIRIMDPD VITGYNIQNF DLPYLISRAQ TLKVPGFPLL
GRVIGLRSNI RESSFQSRQT GRRDSKVVSM VGRVQMDMLQ VLLREYKLRS YTLNAVSFHF
LGEQKEDVQH SIITDLQNGN DQTRRRLAVY CLKDAFLPLR LLERLMVLVN AMEMARVTGV
PLGYLLSRGQ QVKVVSQLLR QAMRQGLLMP VVKTEGGEDY TGATVIEPLK GYYDVPIATL
DFSSLYPSIM MAHNLCYTTL LRPGAAQKLG LTEDQFIKTP TGDEFVKASV RKGLLPQILE
NLLSARKRAK AELAKETDPL RRQVLDGRQL ALKVSANSVY GFTGAQVGRL PCLEISQSVT
GFGRQMIEKT KQLVETKYTV ENGYSTSAKV VYGDTDSVMC RFGVSSVAEA MALGREAADW
VSGHFPSPIR LEFEKVYFPY LLISKKRYAG LLFSSRPDAH DRMDCKGLEA VRRDNCPLVA
NLVTASLRRL LIDRDPSGAV AHAQDVISDL LCNRIDISQL VITKELTRAA ADYAGKQAHV
ELAERMRKRD PGSAPSLGDR VPYVIISAAK GVAAYMKSED PLFVLEHSLP IDTQYYLEQQ
LAKPLLRIFE PILGEGRAEA VLLRGDHTRC KTVLTGKVGG LLAFAKRRNC CIGCRTVLSH
QGAVCKFCQP RESELYQKEV SHLSALEERF SRLWTQCQRC QGSLHEDVIC TSRDCPIFYM
RKKVRKDLED QERLLRRFGP PGPEAW
