POLB Gene

POLB — DNA Polymerase Beta

Introduction

Polb Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

DNA Polymerase Beta (POLB) is a key enzyme in base excision repair (BER), responsible for filling in short gaps in DNA during repair synthesis. It is the smallest eukaryotic DNA polymerase and plays a crucial role in maintaining genomic integrity. [@dna2012]

<div class="infobox infobox-gene"> [@base2006]
<table> [@dna2010]
<tr><th colspan="2" style="background:#e8f4ea;">Gene Information</th></tr> [@dna2011]
<tr><td><strong>Gene Symbol</strong></td><td>POLB</td></tr>
<tr><td><strong>Full Name</strong></td><td>DNA Polymerase Beta</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>8p11.23</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>5423</td></tr>
<tr><td><strong>OMIM ID</strong></td><td>174760</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000067191</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>P06746</td></tr>
<tr><td><strong>Protein</strong></td><td>DNA Polymerase Beta</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Normal Function

DNA Polymerase Beta is essential for:

Base Excision Repair (BER)

...

POLB — DNA Polymerase Beta

Introduction

Polb Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

DNA Polymerase Beta (POLB) is a key enzyme in base excision repair (BER), responsible for filling in short gaps in DNA during repair synthesis. It is the smallest eukaryotic DNA polymerase and plays a crucial role in maintaining genomic integrity. [@dna2012]

<div class="infobox infobox-gene"> [@base2006]
<table> [@dna2010]
<tr><th colspan="2" style="background:#e8f4ea;">Gene Information</th></tr> [@dna2011]
<tr><td><strong>Gene Symbol</strong></td><td>POLB</td></tr>
<tr><td><strong>Full Name</strong></td><td>DNA Polymerase Beta</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>8p11.23</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>5423</td></tr>
<tr><td><strong>OMIM ID</strong></td><td>174760</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000067191</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>P06746</td></tr>
<tr><td><strong>Protein</strong></td><td>DNA Polymerase Beta</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Normal Function

DNA Polymerase Beta is essential for:

Base Excision Repair (BER)

• Fills single-nucleotide gaps after base removal by DNA glycosylases
• 5'-dRP lyase activity removes damaged nucleotides
• Functions in both short-patch and long-patch BER pathways
• Essential for repair of oxidative DNA damage

DNA Synthesis

• Template-directed DNA synthesis
• 5'→3' polymerase activity
• Error-prone compared to replicative polymerases
• Accuracy influenced by accessory factors

Interaction with BER Proteins

• Interacts with XRCC1, DNA ligase III, and PARP1
• Forms multi-protein repair complexes
• Regulated by post-translational modifications

Expression Pattern

• Ubiquitously expressed in all tissues
• Higher activity in proliferating cells
• Expressed in all brain regions
• Increased expression in response to oxidative stress

Disease Associations

Alzheimer's Disease

• POLB activity significantly reduced in AD brain tissue^[1]
• Impaired BER contributes to neuronal DNA damage accumulation
• Potential therapeutic target for enhancing DNA repair

Parkinson's Disease

• Oxidative DNA damage accumulation in dopaminergic [neurons](/entities/neurons)
• POLB polymorphisms associated with PD risk
• May contribute to progressive neuronal loss

Aging

• Declining BER capacity with age
• Accumulation of DNA mutations and strand breaks
• Contributes to age-related neurodegeneration

Cancer

• POLB mutations found in some cancers
• Altered fidelity in tumor cells
• Potential therapeutic target

Therapeutic Targeting

| Approach | Status | Description |
|----------|--------|-------------|
| POLB inhibitors | Preclinical | Cancer therapy |
| BER enhancers | Research | Neuroprotection |
| Gene therapy | Preclinical | POLB delivery |

Gene Structure

The POLB gene spans approximately 30 kb on chromosome 8p12 and contains:

• 14 Exons: Ranging from 56 to 2,500 bp
• Alternative Splicing: Produces multiple transcript variants
• Promoter Region: Contains binding sites for transcription factors including SP1, AP-1, and p53

Expression Pattern

POLB is expressed in all human tissues with highest levels in:

• Bone marrow
• Testis
• Peripheral blood leukocytes
• Brain (neurons and glia)

Expression is cell cycle-regulated, with peaks during G1/S phase transition.

Polymorphisms and Variants

Several POLB polymorphisms have been associated with:

• Cancer risk (reduced activity variants)
• Neurological disease susceptibility
• Response to DNA-damaging chemotherapeutics

Animal Models

Knockout mouse studies reveal:

• Embryonic lethality in Polb-/- mice
• Severe neurological defects in conditional knockouts
• Increased susceptibility to genotoxic stress

See Also

• [OGG1 Gene](/proteins/ogg1-protein) — DNA glycosylase
• [XRCC1 Gene](/proteins/xrcc1-protein) — BER scaffold
• [DNA Damage Response](/mechanisms/dna-damage-response)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [NCBI Gene: POLB](https://www.ncbi.nlm.nih.gov/gene/5423)
• [UniProt: P06746](https://www.uniprot.org/uniprot/P06746)
• [Ensembl: POLB](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000067191)

Background

The study of Polb Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

Canugovi C, et al, DNA polymerase beta deficiency in Alzheimer's disease (2018)

[^2] Sobol RW, et al, DNA polymerase beta in neurodegeneration (2012)

[^3] Cabelof DC, et al, Base excision repair deficiency as a chemoprevention target (2006)

[^4] Wilson DM 3rd, et al, DNA polymerases and aging (2010)

[^5] Lange SS, et al, DNA polymerase beta: cellular functions and disease (2011)