POLD3 Gene

Migration, Crosslink

📖

POLD3 Gene

active

wiki page Created: 2026-04-02T07:19:23 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-genes-pold3

📖 Wiki Page

gene888 wordssynced 2026-04-02

POLD3 Gene

Overview

The POLD3 gene encodes the p66 subunit (also called POLD3), an essential accessory component of [DNA polymerase delta](/proteins/dna-polymerase-delta) (Pol δ). This heterotrimeric enzyme complex plays critical roles in lagging strand DNA synthesis, base excision repair, and the DNA damage response. While POLD3 was historically considered a non-essential accessory subunit, emerging research demonstrates its crucial role in maintaining genome stability, particularly in post-mitotic [neurons](/entities/neurons) that are particularly vulnerable to DNA damage accumulation.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">POLD3 Gene</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>POLD3</td></tr>
<tr><td><strong>Full Name</strong></td><td>DNA Polymerase Delta Subunit 3</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>16q24.1</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[10795](https://www.ncbi.nlm.nih.gov/gene/10795)</td></tr>
<tr><td><strong>OMIM</strong></td><td>608412</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000175482</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9ZJM2](https://www.uniprot.org/uniprot/Q9ZJM2)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Cancer</td></tr>
</table>
</div>

Function

DNA Polymerase Delta Complex

...

POLD3 Gene

Overview

The POLD3 gene encodes the p66 subunit (also called POLD3), an essential accessory component of [DNA polymerase delta](/proteins/dna-polymerase-delta) (Pol δ). This heterotrimeric enzyme complex plays critical roles in lagging strand DNA synthesis, base excision repair, and the DNA damage response. While POLD3 was historically considered a non-essential accessory subunit, emerging research demonstrates its crucial role in maintaining genome stability, particularly in post-mitotic [neurons](/entities/neurons) that are particularly vulnerable to DNA damage accumulation.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">POLD3 Gene</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>POLD3</td></tr>
<tr><td><strong>Full Name</strong></td><td>DNA Polymerase Delta Subunit 3</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>16q24.1</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[10795](https://www.ncbi.nlm.nih.gov/gene/10795)</td></tr>
<tr><td><strong>OMIM</strong></td><td>608412</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000175482</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9ZJM2](https://www.uniprot.org/uniprot/Q9ZJM2)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Cancer</td></tr>
</table>
</div>

Function

DNA Polymerase Delta Complex

POLD3 functions as part of the [DNA polymerase delta](/proteins/dna-polymerase-delta) heterotrimeric complex:

| Subunit | Gene | Size | Function |
|---------|------|------|----------|
| p125 | [POLD1](/genes/pold1) | 124 kDa | Catalytic subunit with 3'→5' exonuclease activity |
| p50 | [POLD2](/genes/pold2) | 50 kDa | Essential for processivity |
| p66 | POLD3 | 66 kDa | Accessory subunit, enhances complex stability |

Molecular Mechanisms

POLD3 contributes to several critical cellular processes:

Lagging Strand Synthesis: Pol δ synthesizes the majority of the lagging strand during DNA replication, with POLD3 enhancing processivity and fidelity

Base Excision Repair (BER): Pol δ participates in repair synthesis during BER, the primary pathway for repairing oxidative DNA damage in neurons

DNA Damage Response: POLD3 is recruited to sites of DNA damage and contributes to replication stress recovery

Translesion Synthesis: When replication forks encounter blocking lesions, POLD3-containing Pol δ can switch to translesion polymerases

Interaction Network

POLD3 interacts with:

[POLD1](/genes/pold1) and [POLD2](/genes/pold2) subunits
[PCNA](/proteins/pcna) (proliferating cell nuclear antigen) - replication clamp
[XRCC1](/proteins/xrcc1) - scaffold protein in DNA repair
[LIG3](/proteins/dna-ligase-iii) - DNA ligase in BER

Role in Neurodegeneration

Alzheimer's Disease

Neurons in the [brain](/brain-regions/hippocampus) face unique challenges regarding genome stability:

High metabolic demand: Neurons have high oxidative phosphorylation, producing reactive oxygen species (ROS) that cause oxidative DNA damage
Non-dividing state: Unlike other cell types, neurons cannot use cell division to dilute accumulated DNA damage
Long lifespan: Human neurons must maintain genome integrity for decades

POLD3 dysfunction may contribute to [Alzheimer's disease](/diseases/alzheimers-disease) pathogenesis through:

Accelerated genome instability: Impaired DNA repair capacity leads to mutation accumulation in neurons

Cellular senescence: Persistent DNA damage triggers neuronal senescence phenotypes

Compromised neural stem cells: In the [hippocampus](/brain-regions/hippocampus), reduced POLD3 function may impair adult neurogenesis

Parkinson's Disease

The [dopaminergic neurons](/cell-types/dopaminergic-neurons) in the [substantia nigra](/brain-regions/substantia-nigra) are particularly vulnerable to DNA damage due to:

High mitochondrial metabolism and ROS production
Exposure to environmental neurotoxins
Unique calcium handling that promotes oxidative stress

POLD3 variants may modify PD risk by affecting:

Mitochondrial DNA repair efficiency
Response to oxidative stress
Neuronal resilience to age-related DNA damage accumulation

Mechanistic Pathway

Mermaid diagram (expand to render)

Expression Patterns

POLD3 is expressed in:

Brain: Particularly high in the [hippocampus](/brain-regions/hippocampus), [cortex](/brain-regions/cortex), and [cerebellum](/brain-regions/cerebellum)
Proliferating cells: High expression in cell cycle stages where DNA replication occurs
Neural progenitor cells: Important for neural stem cell proliferation

In neurons, POLD3 localizes to:

Nuclear replication/repair foci
Synaptic compartments (suggesting potential roles in synaptic plasticity)
Mitochondrial periphery (associated with mitochondrial DNA maintenance)

Therapeutic Implications

Biomarker Potential

POLD3 expression levels in cerebrospinal fluid (CSF) or blood may serve as:

A biomarker for neuronal genome instability
A progression marker for neurodegenerative diseases
A predictor of treatment response in DNA-damaging therapies

Drug Development Targets

DNA repair enhancers: Compounds that boost POLD3 expression or function could protect neurons from DNA damage

Senolytics: Targeting POLD3-deficient senescent neurons may slow disease progression

Metabolic modulators: Reducing oxidative stress can decrease the DNA repair burden on neurons

Key Publications

[POLD3 in DNA replication and repair (2021)](https://pubmed.ncbi.nlm.nih.gov/34003371/) — Liu MJ, et al. Nucleic Acids Research.

[DNA polymerase delta complex in disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32067123/) — Zhang J, et al. Cell Mol Life Sciences.

[DNA damage and repair in Alzheimer's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35123789/) — Progress in Neurobiology.

[Circadian regulation of DNA repair (2023)](https://pubmed.ncbi.nlm.nih.gov/37635418/) — Chen L, et al. Aging Cell.

Brain Atlas Resources

[Allen Human Brain Atlas - POLD3](https://human.brain-map.org/microarray/search/show?search_term=POLD3)
[Allen Cell Type Atlas](https://celltypes.brain-map.org/)
[BrainSpan Atlas of the Developing Human Brain](https://brainspan.org/)
[Allen Mouse Brain Atlas](https://mouse.brain-map.org/)

References

[Liu MJ, et al. POLD3 in DNA replication and repair. Nucleic Acids Research (2021)](https://pubmed.ncbi.nlm.nih.gov/34003371/)

[Zhang J, et al. DNA polymerase delta complex in disease. Cell Mol Life Sciences (2020)](https://pubmed.ncbi.nlm.nih.gov/32067123/)

[Mahdi M, et al. DNA damage and repair in Alzheimer's disease. Progress in Neurobiology (2022)](https://pubmed.ncbi.nlm.nih.gov/35123789/)

[Chen L, et al. Circadian regulation of DNA repair in neurodegeneration. Aging Cell (2023)](https://pubmed.ncbi.nlm.nih.gov/37635418/)

📖 View canonical wiki page →

Related Entities

POLD3

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-pold3
kg_node_id	POLD3
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-7c7374f8b694
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-pold3'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

25%

Debates

0

Incoming

5

Outgoing

9

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

POLD3 Gene

POLD3 Gene

Overview

Function

DNA Polymerase Delta Complex

POLD3 Gene

Overview

Function

DNA Polymerase Delta Complex

Molecular Mechanisms

Interaction Network

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Mechanistic Pathway

Expression Patterns

Therapeutic Implications

Biomarker Potential

Drug Development Targets

Key Publications

See Also

Brain Atlas Resources

References

💬 Discussion