DNA polymerase delta subunit 3

UniProt Q15054 Organism Homo sapiens Gene KIAA0039, POLD3

Also known as: KIAA0039, POLD3

Function

Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex. As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA. Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4. Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also 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. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites. Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion. Also involved in TLS, as a component of the tetrameric DNA polymerase zeta complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7.

Classification

Family (Pfam): PF09507 CDC27
InterPro: POLD3, POLD3_sf
Functional cluster: Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 9

1U76 X-ray 2.60A
2N1G NMR
3E0J X-ray 3.00A
6S1M EM 4.27A
6S1N EM 4.86A
6S1O EM 8.10A
6TNY EM 3.08A
6TNZ EM 4.05A
9EKB EM 3.65A

A predicted model is available from AlphaFold.

Gene Ontology · 13

Disease associations

immunodeficiency 122 MONDO:0971151

Drugs targeting this protein · 6

FLUDARABINE PHOSPHATE inhibitor
GEMCITABINE HYDROCHLORIDE inhibitor
CLOFARABINE inhibitor
TROXACITABINE inhibitor
ASPACYTARABINE inhibitor
CYTARABINE inhibitor

Related proteins · sequence + function similarity

DNA polymerase delta subunit 3 0.98
DNA polymerase delta subunit 3 0.96
DNA polymerase delta subunit 3 0.96
RAD51-associated protein 1 0.68
RAD51-associated protein 1 0.65
RAD51-associated protein 1 0.64
Zinc finger CCCH domain-containing protein 11A 0.63
Zinc finger CCCH domain-containing protein 11A 0.62
Nibrin 0.62
E3 ubiquitin-protein ligase RAD18 0.62
Nibrin 0.62
Nuclear pore complex protein Nup153 0.61

Co-cited proteins · studied together in the literature

DNA polymerase delta subunit 3 2 shared papers
DNA polymerase delta subunit 2 14 shared papers
DNA polymerase delta subunit 4 11 shared papers
DNA polymerase delta subunit 3 1 shared papers
DNA polymerase delta catalytic subunit 13 shared papers
Translesion synthesis protein REV1 1 shared papers
DNA sliding clamp PCNA 5 shared papers
DNA polymerase eta 2 shared papers
DNA polymerase zeta catalytic subunit 1 shared papers
DNA polymerase delta catalytic subunit 1 shared papers
Chromosome transmission fidelity protein 18 homolog 1 shared papers
Cyclin-dependent kinase inhibitor 1 1 shared papers

Literature · 41 cited papers

Human Autosomal Recessive DNA Polymerase Delta 3 Deficiency Presenting as Omenn Syndrome. J. Clin. Immunol. · 2023
POLD3 deficiency is associated with severe combined immunodeficiency, neurodevelopmental delay, and hearing impairment. Clin. Immunol. · 2023
Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
In vivo evidence for translesion synthesis by the replicative DNA polymerase delta. Nucleic Acids Res. · 2016
Interaction between the Rev1 C-Terminal Domain and the PolD3 Subunit of Polzeta Suggests a Mechanism of Polymerase Exchange upon Rev1/Polzeta-Dependent Translesion Synthesis. Biochemistry · 2016
The POLD3 subunit of DNA polymerase delta can promote translesion synthesis independently of DNA polymerase zeta. Nucleic Acids Res. · 2015
Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
Human Pol zeta purified with accessory subunits is active in translesion DNA synthesis and complements Pol eta in cisplatin bypass. Proc. Natl. Acad. Sci. U.S.A. · 2014
Break-induced replication repair of damaged forks induces genomic duplications in human cells. Science · 2014
Dynamics of enzymatic interactions during short flap human Okazaki fragment processing by two forms of human DNA polymerase delta. DNA Repair · 2013
A novel function of CRL4(Cdt2): regulation of the subunit structure of DNA polymerase delta in response to DNA damage and during the S phase. J. Biol. Chem. · 2013
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
… and 29 more in the literature graph

A document in the lmmol reference corpus — open public data (UniProt, GO, PDB, the literature graph) rendered as a single cross-linked page. Hover any link to preview its target.