Gene Ontology annotation through association of InterPro records with GO terms.
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.
Gene Ontology annotation based on curation of immunofluorescence data
Combined Automated Annotation using Multiple IEA Methods.
Mediation of proliferating cell nuclear antigen (PCNA)-dependent DNA replication through a conserved p21(Cip1)-like PCNA-binding motif present in the third subunit of human DNA polymerase delta.
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POLD2 (p50) directly interacts with the N-terminus of POLD3 (p66), placing POLD2 at the structural core of Polδ and linking the complex to PCNA via POLD3's PIP box.
"the third subunit of human DNA polymerase delta, p66, interacts with PCNA through a canonical PCNA-binding sequence located in its C terminus"
Reconstitution and characterization of the human DNA polymerase delta four-subunit holoenzyme.
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Polδ was reconstituted as the four-subunit holoenzyme (POLD1/p125 + POLD2/p50 + POLD3/p66 + POLD4/p12); POLD2 is a core component.
"Reconstitution and characterization of the human DNA polymerase delta four-subunit holoenzyme."
Identification of a novel protein, PDIP38, that interacts with the p50 subunit of DNA polymerase delta and proliferating cell nuclear antigen.
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PDIP38 (POLDIP2) was identified as a direct binding partner of POLD2 (p50).
"Identification of a novel protein, PDIP38, that interacts with the p50 subunit of DNA polymerase delta and proliferating cell nuclear antigen."
Human Werner helicase interacting protein 1 (WRNIP1) functions as a novel modulator for DNA polymerase delta.
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WRNIP1 physically interacts with and modulates Polδ activity.
"the purified human WRNIP1 complex interacted physically with human DNA polymerase delta (pol delta), stimulating its DNA synthesis activity more than fivefold in the presence or absence of proliferating cell nuclear antigen"
An in vivo analysis of the localisation and interactions of human p66 DNA polymerase delta subunit.
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POLD3 (p66) interacts with POLD2 (p50) via its N-terminus and with PCNA via its C-terminus; the POLD2-POLD3 interaction is essential for Polδ function.
"we have mapped the interaction domains for binding to the p50 polymerase delta subunit and with PCNA to the N-terminus and the C-terminus of p66"
Functional roles of p12, the fourth subunit of human DNA polymerase delta.
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POLD4 (p12) is tightly associated with POLD2 (p50), and may stabilize the POLD1-POLD2 interaction within the Polδ heterotetramer.
"which is tightly associated with the p50 subunit"
The p12 subunit of human polymerase delta modulates the rate and fidelity of DNA synthesis.
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Reconstituted four-subunit Polδ holoenzyme (containing POLD2) catalyzes template-directed DNA synthesis with kinetics modulated by p12.
"This study examines the role of the p12 subunit in the function of the human DNA polymerase δ (Pol δ) holoenzyme by comparing the kinetics of DNA synthesis and degradation catalyzed by the four subunit complex"
DNA polymerase δ and ζ switch by sharing accessory subunits of DNA polymerase δ.
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POLD2 (the B-subunit) binds equally well to the catalytic subunits of either Polδ (POLD1) or Polζ (REV3); the highly conserved CTDs of POLD1 and REV3 contain a [4Fe-4S] cluster that mediates binding to POLD2 and is critical for UV mutagenesis.
"( i ) the B-subunit of Pol δ binds equally well to the catalytic subunit of either Pol δ or Pol ζ; ( ii ) the CTDs of Pol δ and Pol ζ contain a [4Fe-4S] cluster, which is critical for binding to the B-subunit and for UV light-induced mutagenesis"
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Pol δ↔Pol ζ switching at lesions occurs via exchange of catalytic subunits on a preassembled platform of the shared accessory subunits POLD2 and POLD3.
"we propose that Pol switches at replication-blocking lesions occur by the exchange of the Pol δ and Pol ζ catalytic subunits on a preassembled complex of accessory proteins retained on DNA during translesion DNA synthesis."
Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass.
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Human Pol ζ purifies as a four-subunit complex (Pol ζ4 = REV3-REV7-POLD2- POLD3) that is far more efficient and processive at bypassing cisplatin lesions than two-subunit Pol ζ2 (REV3-REV7).
"The purified four-subunit Pol ζ4 (Rev3–Rev7–PolD2–PolD3) is much more efficient and more processive at bypassing a 1,2-intrastrand d(GpG)-cisplatin cross-link than the two-subunit Pol ζ2 (Rev3–Rev7)."
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The POLD2-POLD3 cocrystal structure presents a negatively charged surface without obvious DNA-binding features; POLD2 contributes to Pol ζ4 activity via protein-protein contacts rather than direct DNA binding.
"The cocrystal structure of human PolD2 and the NTD of PolD3 has been determined ( 35 ) and shows a primarily negatively charged molecular surface without obvious features for DNA binding."
FF483-484 motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance.
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POLD2 is the direct binding partner of the FF483-484 motif of human Polη; this interaction is required for efficient TLS at CPDs and for survival of XPV cells after UV irradiation, supporting a Polη↔Polδ polymerase-switching mechanism.
"Only POLD2, the B-subunit of Polδ, was found to bind to Polη in a two-hybrid experiment and this interaction was further confirmed in a pull-down assay. Mutation of the FF483–484 motif of Polη (designated F1 motif) involved in the interaction with POLD2 reduces the Polη ability to perform TLS catalyzed by cellular extracts in vitro and to rescue the UV sensitivity of XPV fibroblasts."
A fluorescent bimolecular complementation screen reveals MAF1, RNF7 and SETD3 as PCNA-associated proteins in human cells.
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
Architecture of the human interactome defines protein communities and disease networks.
Polymerase δ deficiency causes syndromic immunodeficiency with replicative stress.
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Polδ is a heterotetramer of POLD1 (catalytic) + POLD2 + POLD3 + POLD4 and is essential for eukaryotic genome duplication on both leading and lagging strands.
"The mammalian polymerase δ complex is a heterotetramer consisting of the catalytic subunit POLD1 and the accessory subunits POLD2, POLD3, and POLD4"
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POLD2 plays a central structural role in interacting with both POLD1 and POLD3, and POLD2/POLD3 are shared with the Pol ζ translesion complex.
"The specific function of the POLD2 subunit has been poorly explored, despite its central structural role in interacting with both POLD1 and POLD3 ( 12 ). Interestingly, POLD2 and POLD3 participate in translesion synthesis (TLS) via their interaction with the polymerase ζ complex"
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A homozygous POLD2 p.Asp293Asn variant destabilizes the Polδ complex, reduces POLD1/POLD2/POLD3 protein levels, and causes an autosomal-recessive syndrome of replicative stress, neurodevelopmental abnormalities, and combined immunodeficiency; WT POLD2 rescue restores complex stability and reduces 53BP1 bodies.
"In patients from 2 independent pedigrees, we have identified what we believe to be a novel syndrome with reduced functionality of the polymerase δ complex caused by germline biallelic mutations in POLD1 or POLD2 as the underlying etiology of a previously unknown autosomal-recessive syndrome that combines replicative stress, neurodevelopmental abnormalities, and immunodeficiency."
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Mitotic DNA synthesis in response to replication stress requires the sequential action of DNA polymerases zeta and delta in human cells.
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POLD2 (with POLD3) is a shared subunit of Polδ and Polζ4; the two polymerases act sequentially in mitotic DNA synthesis (MiDAS) to complete under-replicated regions, providing a replication-stress context where POLD2 contributes to both replicative and TLS complexes.
"More recently, it was revealed that human Pol ζ can contain 2 subunits in addition to REV3 and REV7, and this holoenzyme is referred to as Pol ζ444. These two additional subunits are POLD2 and POLD3, both of which are also subunits of human Pol δ."
PARP1 and POLD2 as prognostic biomarkers for multiple myeloma in autologous stem cell transplant.
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POLD2 is part of the base excision repair (BER) gene set upregulated in multiple myeloma; high POLD2 expression in ASCT-treated patients is associated with worse overall survival, consistent with POLD2's role in long-patch BER repair synthesis.
"Key proteins involved in the BER pathway, including APEX1/2, XRCC1, PARP1, POLD2, have been associated with chemoresistance across many cancer types."
Association of Mutations in Replicative DNA Polymerase Genes with Human Disease: Possible Application of Drosophila Models for Studies.
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Review confirming biallelic POLD2 mutations (including D293N) cause an autosomal-recessive syndrome with replicative stress and immunodeficiency, consistent with POLD2's central role in Polδ complex stability.
"Biallelic mutations in POLD1 or POLD2 are also found in patients manifesting an autosomal recessive syndrome that combines replicative stress, neurodevelopmental abnormalities and immunodeficiency. Homozygous missense variant D293N was found in the POLD2 gene."
The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity.
POLD3 as Controller of Replicative DNA Repair.
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Review highlighting that the POLD2-POLD3 interface is essential for normal Polδ function; CysA/CysB motifs of POLD1 (not POLD2 as previously stated) mediate POLD1-POLD2 interactions, with POLD3 modulating catalytic activity via this interaction.
"The interaction between POLD3 and POLD2 is essential for normal Polδ function — mutations of the POLD2-POLD3 interaction region in S. cerevisiae cause the cdc27 cold sensitive phenotype. We speculate that modulation of POLD1 catalytic activity by POLD3 may be by influencing POLD2-POLD1 interactions, centered at CysA and CysB motifs of POLD1."
Prospects of POLD1 in Human Cancers: A Review.
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Review establishing Polδ subunit composition (POLD1/2/3/4) and roles in cancer.
"Human Polδ holoenzyme has been believed to be a heterotetramer in unstressed, non-dividing cells composed of a catalytic subunit (POLD1) and three accessory subunits, POLD2 (p50), POLD3 (p66/p68), and POLD4 (p12)"
Cloning of the cDNAs for the small subunits of bovine and human DNA polymerase delta and chromosomal location of the human gene (POLD2).
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Identified POLD2 as the small (~50 kDa) subunit of human DNA polymerase delta and mapped the gene to human chromosome 7.
"cDNAs encoding the small subunit of bovine and human DNA polymerase delta have been cloned and sequenced. The predicted polypeptides, 50,885 and 51,289 Daltons, respectively, are 94% identical"
FEN1 bound to PCNA and APEX1 cleaves flap ssDNA
PCNA:POLD,POLE:RPA:RFC and FEN1 bind APEX1
POLD,POLE-mediated DNA strand displacement synthesis
LIG1 binds APEX1 and PCNA at SSB
Formation of the Flap Intermediate on the C-strand
Removal of RNA primer and dissociation of RPA and Dna2 from the C-strand
Formation of C-strand Okazaki fragments
RPA binds to the Flap on the C-strand
Removal of remaining Flap from the C-strand
Formation of Processive Complex on the C-strand of the telomere
Recruitment of DNA2 endonuclease to the C strand
Joining of adjacent Okazaki fragments of the C-strand
Disassociation of Processive Complex and Completed Telomere End
DNA polymerase delta polymerizes DNA across single stranded gap
LIG1 bound to APEX1 and PCNA ligates SSB
LIG1, APEX1 and PCNA:POLD,POLE:RPA:RFC dissociate from repaired DNA
PCNA-containing replication complex binds damaged dsDNA
RAD18:UBE2B or RBX1:CUL4:DDB1:DTL ubiquitin ligase complex binds PCNA:POLD,POLE:RPA:RFC associated with damaged dsDNA
RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA
POLD,POLE binds deISGylated PCNA after TLS
POLD,POLE complete replication of damaged DNA after TLS
DNA polymerases delta, epsilon or kappa bind the GG-NER site
3'-incision of DNA by ERCC5 (XPG) in GG-NER
Ligation of newly synthesized repair patch to incised DNA in GG-NER
Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in GG-NER
Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER
DNA polymerases delta, epsilon or kappa bind the TC-NER site
3' incision by ERCC5 (XPG) in TC-NER
Ligation of newly synthesized repair patch to incised DNA in TC-NER
Formation of Processive Complex
Formation of Okazaki fragments
Formation of the Flap Intermediate
Recruitment of Dna2 endonuclease
Removal of RNA primer and dissociation of RPA and Dna2
Removal of remaining Flap
Deep research on POLD2 function (falcon, Edison Scientific Literature, 2026-05-29)
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POLD2 is an essential non-catalytic subunit of the heterotetrameric DNA polymerase delta, with a central structural role in mediating POLD1-POLD3 interactions and supporting holoenzyme assembly/stability.
"POLD2 functions as an **essential non-catalytic subunit** of the Polδ holoenzyme, supporting assembly, stability, and productive interactions among subunits required for high-fidelity DNA synthesis in nuclear DNA replication and repair-associated synthesis."
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POLD2 (and POLD3) are also incorporated into Pol ζ4 (REV3-REV7-POLD2-POLD3), providing a polymerase-switching platform for translesion synthesis and mitotic DNA synthesis.
"POLD2 is relevant because it is part of Polδ and is also shared with **Polζ4** (a translesion polymerase complex), supporting polymerase switching and stress-tolerant DNA synthesis."
Deep research on POLD2 function (perplexity)