DPOD1_MESAU
ID DPOD1_MESAU Reviewed; 1103 AA.
AC P97283; P97284;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 121.
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 Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liu Z., Mishra N.C.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
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. Stimulated in the presence of PCNA (By similarity). This
CC stimulation is further increased in the presence of KCTD13/PDIP1, most
CC probably via direct interaction between KCTD13 and POLD2 (By
CC similarity). {ECO:0000250|UniProtKB:P28339,
CC ECO:0000250|UniProtKB:P28340}.
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. Within Pol-delta4, directly
CC interacts with POLD2 and POLD4. Following genotoxic stress by DNA-
CC damaging agents, such as ultraviolet light and methyl methanesulfonate,
CC or by replication stress induced by treatment with hydroxyurea or
CC aphidicolin, Pol-delta4 is converted into a trimeric form of the
CC complex (Pol-delta3) by POLD4 degradation. Pol-delta3 is the major form
CC at S phase replication sites and DNA damage sites. POLD1 displays
CC different catalytic properties depending upon the complex it is found
CC in. It exhibits higher proofreading activity and fidelity than Pol-
CC delta4, making it particularly well suited to respond to DNA damage.
CC Directly interacts with PCNA, as do POLD3 and POLD4; this interaction
CC stimulates Pol-delta4 polymerase activity. As POLD2 and POLD4, directly
CC interacts with WRNIP1; this interaction stimulates DNA polymerase
CC delta-mediated DNA synthesis, independently of the presence of PCNA.
CC This stimulation may be due predominantly to an increase of initiation
CC frequency and also to increased processivity. Also observed as a
CC 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. The DNA polymerase delta complex
CC interacts with POLDIP2; this interaction is probably mediated through
CC direct binding to POLD2. Interacts with CIAO1. Interacts with POLDIP2
CC (By similarity). {ECO:0000250|UniProtKB:P28340}.
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; U83704; AAB47254.1; -; mRNA.
DR EMBL; U83705; AAB47255.1; -; mRNA.
DR AlphaFoldDB; P97283; -.
DR SMR; P97283; -.
DR STRING; 10036.XP_005084828.1; -.
DR eggNOG; KOG0969; Eukaryota.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0043232; C:intracellular non-membrane-bounded organelle; IEA:UniProt.
DR GO; GO:0031981; C:nuclear lumen; IEA:UniProt.
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; IEA:UniProtKB-KW.
DR GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0034644; P:cellular response to UV; ISS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; ISS:UniProtKB.
DR GO; GO:0070987; P:error-free translesion synthesis; ISS:UniProtKB.
DR GO; GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB.
DR Gene3D; 1.10.132.60; -; 1.
DR Gene3D; 3.30.420.10; -; 1.
DR Gene3D; 3.90.1600.10; -; 2.
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 2: Evidence at transcript level;
KW 4Fe-4S; DNA damage; DNA excision; DNA repair; DNA replication; DNA-binding;
KW DNA-directed DNA polymerase; Exonuclease; Hydrolase; Iron; Iron-sulfur;
KW Isopeptide bond; Metal-binding; Methylation; Nuclease;
KW Nucleotidyltransferase; Nucleus; Reference proteome; Transferase;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1103
FT /note="DNA polymerase delta catalytic subunit"
FT /id="PRO_0000046443"
FT ZN_FING 1008..1025
FT /note="CysA-type"
FT REGION 1..29
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 1054..1072
FT /note="CysB motif"
FT BINDING 1008
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1011
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1022
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 1054
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 1057
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 1067
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 1072
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 570
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P28340"
FT VARIANT 64
FT /note="Missing (in delta')"
FT VARIANT 386
FT /note="P -> S (in delta')"
SQ SEQUENCE 1103 AA; 123466 MW; 34AB5BF72DE53011 CRC64;
MDFKRRQGPG PGVPPKRARG GLWDEDEPSQ FEENLALLEE IEAENRLQEA EEELQLPPQG
PAGGQFSTAD IDPRWKRPAL CALDPNTEPL IFQQLEIDHY VGSAVPLPGG PPTSCNSVPI
LRAFGVTDEG FSVCCHIHGF APYFYTPAPP GFGAEHLSDL QRELSTAISR DQRGGKELSG
PAVLAIELCS RESMFGYHGH GPSPFLRITL ALPRLVAPAR RLLEQGIRVP GLGTPSFAPY
EANVDFEIRF MVDADIVGCN WLELPAGKYV WRTEKKATQC QLEVDVLWSD VISHPPEGQW
QRIAPLRVLS FDIECAGRKG IFPEPERDPV IQICSLGLRW GEPEPFLRLA LTLRPCAPIL
GAKVQSYERE EDLLQAWPNF ILAMDPDVIT GYNIQNFDLP YLISRAQTLK VDRFPFLGRV
TGLRSNIRDS SFQSRQVGRR DSKVVSMVGR VQMDMLQVLL REHKLRSYTL NAVSFHFLGE
QKEDVQHSII TDLQNGNEQT RRRLAVYCLR DAFLPLRLLE RLMVLVNNVE MARVTGVPLG
YLLSRGQQVK VVSQLLRQAM RQGLLMPVVK TEGGEDYTGA TVIEPLKGYY DVPIATLDFS
SLYPSIMMAH NLCYTTLLRP GAAQKLGLKP DEFIKTPTGD EFVKSSVRKG LLPQILENLL
SARKRAKAEL AQETDPLRRQ VLDGRQLALK VSANSVYGFT GAEVGKLPCL EISQSVTGFG
RQMIEKTKQL VESKYTLENG YNANAKVVYG DTDSVMCRFG VSSVAEAMSL GREAANWVSS
HFPSPIRLEF EKVYFPYLLI SKKRYAGLLF SSQPDTHDRM DCKGLEAVRR DNCPLVANLV
TSSLRRILVD RDPDGAVAHA KDVISDLLCN RIDISQLVIT KELTRAAADY AGKQAHVELA
ERMRKRDPGS APSLGDRVPY VIIGAAKGVA AYMKSEDPLF VLEHSLPIDT QYYLGQQLAK
PLLRIFEPIL GEGRAESVLL RGDHTRCKTV LTSKVGGLLA FTKRRNCCIG CRSVINHQGA
VCEFCQPRES ELYQKEVSHL NALEERFSRL WTQCQRCQGS LHEDVICTSR DCPIFYMRKK
VRKDLEDQER LLQRFGPPGP EAW
