P97283 · DPOD1_MESAU

Function

function

As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities. Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4. Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated. Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine, 8oxoG or abasic sites.

Miscellaneous

In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.

Catalytic activity

Cofactor

[4Fe-4S] cluster (UniProtKB | Rhea| CHEBI:49883 )

Note: Binds 1 [4Fe-4S] cluster.

Activity regulation

Regulated by alteration of quaternary structure. Exhibits burst rates of DNA synthesis are about 5 times faster in the presence of POLD4 (Pol-delta4 complex) than in its absence (Pol-delta3 complex), while the affinity of the enzyme for its DNA and dNTP substrates appears unchanged. The Pol-delta3 complex is more likely to proofread DNA synthesis because it cleaves single-stranded DNA twice as fast and transfers mismatched DNA from the polymerase to the exonuclease sites 9 times faster compared to the Pol-delta3 complex. Pol-delta3 also extends mismatched primers 3 times more slowly in the absence of POLD4. The conversion of Pol-delta4 into Pol-delta3 is induced by genotoxic stress or by replication stress leading POLD4 degradation. Stimulated in the presence of PCNA (By similarity).
This stimulation is further increased in the presence of KCTD13/PDIP1, most probably via direct interaction between KCTD13 and POLD2 (By similarity).

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site1008Zn2+ (UniProtKB | ChEBI)
Binding site1011Zn2+ (UniProtKB | ChEBI)
Binding site1022Zn2+ (UniProtKB | ChEBI)
Binding site1025Zn2+ (UniProtKB | ChEBI)
Binding site1054[4Fe-4S] cluster (UniProtKB | ChEBI)
Binding site1057[4Fe-4S] cluster (UniProtKB | ChEBI)
Binding site1067[4Fe-4S] cluster (UniProtKB | ChEBI)
Binding site1072[4Fe-4S] cluster (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentdelta DNA polymerase complex
Molecular Function4 iron, 4 sulfur cluster binding
Molecular Functionchromatin binding
Molecular Functiondamaged DNA binding
Molecular FunctionDNA-directed DNA polymerase activity
Molecular Functionexonuclease activity
Molecular Functionmetal ion binding
Molecular Functionnucleotide binding
Biological Processcellular response to UV
Biological ProcessDNA replication
Biological ProcessDNA synthesis involved in DNA repair
Biological Processerror-free translesion synthesis
Biological Processfatty acid homeostasis

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    DNA polymerase delta catalytic subunit
  • EC number
  • Alternative names
    • 3'-5' exodeoxyribonuclease
      (EC:3.1.11.-
      ) . EC:3.1.11.- (UniProtKB | ENZYME | Rhea)

Gene names

    • Name
      POLD1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Cricetidae > Cricetinae > Mesocricetus

Accessions

  • Primary accession
    P97283
  • Secondary accessions
    • P97284

Proteomes

Subcellular Location

Nucleus
Note: Colocalizes with PCNA and POLD3 at S phase replication sites. After UV irradiation, recruited to DNA damage sites within 2 hours, independently on the cell cycle phase, nor on PCNA ubiquitination. This recruitment requires POLD3, PCNA and RFC1-replication factor C complex.

Keywords

Phenotypes & Variants

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variant64in delta'
Natural variant386in delta'

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 2 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, modified residue, cross-link.

TypeIDPosition(s)Description
ChainPRO_00000464431-1103DNA polymerase delta catalytic subunit
Modified residue19Omega-N-methylarginine
Cross-link570Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)

Keywords

Interaction

Subunit

Component of the tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing both DNA polymerase and 3' to 5' proofreading exonuclease activities. Within Pol-delta4, directly interacts with POLD2 and POLD4. Following genotoxic stress by DNA-damaging agents, such as ultraviolet light and methyl methanesulfonate, or by replication stress induced by treatment with hydroxyurea or aphidicolin, Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) by POLD4 degradation. Pol-delta3 is the major form at S phase replication sites and DNA damage sites. POLD1 displays different catalytic properties depending upon the complex it is found in. It exhibits higher proofreading activity and fidelity than Pol-delta4, making it particularly well suited to respond to DNA damage. Directly interacts with PCNA, as do POLD3 and POLD4; this interaction stimulates Pol-delta4 polymerase activity. As POLD2 and POLD4, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA. This stimulation may be due predominantly to an increase of initiation frequency and also to increased processivity. Also observed as a dimeric complex with POLD2 (Pol-delta2). Pol-delta2 is relatively insensitive to the PCNA stimulation (2-5-fold) compared to Pol-delta4 that is stimulated by over 50-fold. The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2. Interacts with CIAO1. Interacts with POLDIP2 (By similarity).
Interacts with RFC1 (By similarity).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, motif, zinc finger.

TypeIDPosition(s)Description
Region1-29Disordered
Motif4-19Nuclear localization signal
Zinc finger1008-1025CysA-type
Motif1054-1072CysB motif

Domain

The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.

Sequence similarities

Belongs to the DNA polymerase type-B family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,103
  • Mass (Da)
    123,466
  • Last updated
    1997-05-01 v1
  • Checksum
    34AB5BF72DE53011
MDFKRRQGPGPGVPPKRARGGLWDEDEPSQFEENLALLEEIEAENRLQEAEEELQLPPQGPAGGQFSTADIDPRWKRPALCALDPNTEPLIFQQLEIDHYVGSAVPLPGGPPTSCNSVPILRAFGVTDEGFSVCCHIHGFAPYFYTPAPPGFGAEHLSDLQRELSTAISRDQRGGKELSGPAVLAIELCSRESMFGYHGHGPSPFLRITLALPRLVAPARRLLEQGIRVPGLGTPSFAPYEANVDFEIRFMVDADIVGCNWLELPAGKYVWRTEKKATQCQLEVDVLWSDVISHPPEGQWQRIAPLRVLSFDIECAGRKGIFPEPERDPVIQICSLGLRWGEPEPFLRLALTLRPCAPILGAKVQSYEREEDLLQAWPNFILAMDPDVITGYNIQNFDLPYLISRAQTLKVDRFPFLGRVTGLRSNIRDSSFQSRQVGRRDSKVVSMVGRVQMDMLQVLLREHKLRSYTLNAVSFHFLGEQKEDVQHSIITDLQNGNEQTRRRLAVYCLRDAFLPLRLLERLMVLVNNVEMARVTGVPLGYLLSRGQQVKVVSQLLRQAMRQGLLMPVVKTEGGEDYTGATVIEPLKGYYDVPIATLDFSSLYPSIMMAHNLCYTTLLRPGAAQKLGLKPDEFIKTPTGDEFVKSSVRKGLLPQILENLLSARKRAKAELAQETDPLRRQVLDGRQLALKVSANSVYGFTGAEVGKLPCLEISQSVTGFGRQMIEKTKQLVESKYTLENGYNANAKVVYGDTDSVMCRFGVSSVAEAMSLGREAANWVSSHFPSPIRLEFEKVYFPYLLISKKRYAGLLFSSQPDTHDRMDCKGLEAVRRDNCPLVANLVTSSLRRILVDRDPDGAVAHAKDVISDLLCNRIDISQLVITKELTRAAADYAGKQAHVELAERMRKRDPGSAPSLGDRVPYVIIGAAKGVAAYMKSEDPLFVLEHSLPIDTQYYLGQQLAKPLLRIFEPILGEGRAESVLLRGDHTRCKTVLTSKVGGLLAFTKRRNCCIGCRSVINHQGAVCEFCQPRESELYQKEVSHLNALEERFSRLWTQCQRCQGSLHEDVICTSRDCPIFYMRKKVRKDLEDQERLLQRFGPPGPEAW

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U83704
EMBL· GenBank· DDBJ
AAB47254.1
EMBL· GenBank· DDBJ
mRNA
U83705
EMBL· GenBank· DDBJ
AAB47255.1
EMBL· GenBank· DDBJ
mRNA

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp