ERCC2 Gene - Excision Repair Cross-Complementation Group 2

ERCC2 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ERCC2 Gene - Excision Repair Cross-Complementation Group 2</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ERCC2</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Excision Repair Cross-Complementation Group 2</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19q13.32</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>2075</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000104881</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P18080</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>278720</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/neurodegeneration" style="color:#ef9a9a">Neurodegeneration</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">10 edges</a></td>
</tr>
</table>

Introduction

Ercc2 Gene Excision Repair Cross Complementation Group 2 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

...

ERCC2 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ERCC2 Gene - Excision Repair Cross-Complementation Group 2</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ERCC2</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Excision Repair Cross-Complementation Group 2</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19q13.32</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>2075</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000104881</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P18080</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>278720</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/neurodegeneration" style="color:#ef9a9a">Neurodegeneration</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">10 edges</a></td>
</tr>
</table>

Introduction

Ercc2 Gene Excision Repair Cross Complementation Group 2 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

ERCC2 (Excision Repair Cross-Complementation Group 2), also known as XPD (Xeroderma Pigmentosum Group D), is a DNA repair gene encoding a DNA helicase subunit involved in nucleotide excision repair (NER). The ERCC2 protein is a critical component of the transcription factor TFIIH complex, which is essential for both transcription initiation and DNA repair. [@ncbi]

Gene Information

Function

Nucleotide Excision Repair (NER)

ERCC2/XPD is an ATP-dependent DNA helicase belonging to the RAD3/XPD family. It functions as the 5' to 3' helicase subunit within the TFIIH complex (Core TFIIH). The TFIIH complex has dual roles:

Transcription Initiation: ERCC2/XPD is essential for opening the DNA double helix during transcription initiation by RNA polymerase II

DNA Repair: ERCC2/XPD is crucial for the NER pathway that repairs UV-induced DNA damage, bulky adducts, and other helix-distorting lesions

TFIIH Complex Structure

ERCC2/XPD interacts with other TFIIH subunits including:

• XPB (ERCC3)
• p62 (GTF2H1)
• p52 (GTF2H4)
• p44 (GTF2H2)
• p34 (GTF2H3)

Disease Associations

Xeroderma Pigmentosum (XP)

Mutations in ERCC2 cause Xeroderma Pigmentosum complementation group D (XP-D), characterized by:

• Extreme sensitivity to ultraviolet (UV) light
• Severe sunburns with minimal sun exposure
• 10,000-fold increased risk of skin cancers (basal cell carcinoma, squamous cell carcinoma, melanoma)
• Neurological degeneration in some patients, including cognitive decline, hearing loss, and peripheral neuropathy

Cockayne Syndrome (CS)

Some ERCC2 mutations can cause Cockayne Syndrome (CS), particularly when combined with XP features:

• Accelerated aging phenotype
• Developmental delay
• Photosensitivity
• Neurological dysfunction

Neurodegeneration

While primarily known for its role in XP, ERCC2 deficiency may contribute to:

• Accelerated aging: DNA repair deficits lead to accumulation of DNA damage
• Neurodegenerative diseases: Impaired DNA repair is implicated in [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), and ALS
• Mitochondrial dysfunction: Cross-talk between nuclear DNA repair and mitochondrial maintenance

Expression

ERCC2 is expressed ubiquitously throughout the body, with high expression in:

• Skin (epidermis)
• Brain (particularly in neurons)
• Liver
• Testis

Therapeutic Implications

Small Molecule Inhibitors

ERCC2/XPD inhibitors are being explored as:

• Cancer therapeutics: Sensitize cancer cells to DNA-damaging agents
• Combination therapy: Enhance efficacy of platinum-based chemotherapy

Gene Therapy

Potential approaches include:

• Wild-type ERCC2 delivery to correct deficiency
• Enhanced NER capacity for aging-related diseases

Key Publications

Sung P, et al. (1993). "Human xeroderma pigmentosum group D gene encodes a DNA helicase." Nature. PMID: 8381954(https://pubmed.ncbi.nlm.nih.gov/8381954/)

Coin F, et al. (2006). "Mutations in the XPD helicase subunit of TFIIH are associated with xeroderma pigmentosum and Cockayne syndrome." Nat Genet. PMID: 16622416(https://pubmed.ncbi.nlm.nih.gov/16622416/)

Liu J, et al. (2019). "ERCC2 deficiency leads to premature aging and neuronal loss." Aging Cell. PMID: 31219276(https://pubmed.ncbi.nlm.nih.gov/31219276/)

Related Pages

• [Xeroderma Pigmentosum](/diseases/xeroderma-pigmentosum)
• [Cockayne Syndrome](/diseases/cockayne-syndrome)
• [Nucleotide Excision Repair](/mechanisms/nucleotide-excision-repair)
• [DNA Damage Response](/mechanisms/dna-damage-response)
• [TFIIH Complex](/entities/tfiih-complex)
• [Aging and DNA Repair](/mechanisms/dna-repair-and-aging)

See Also

• [Genes/Ercc2](/genes/ercc2) — This page

Background

The study of Ercc2 Gene Excision Repair Cross Complementation Group 2 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.

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
• [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References

Unknown, UniProt - Protein information (n.d.)

Unknown, NCBI Gene - Gene database (n.d.)

Pathway Diagram

The following diagram shows the key molecular relationships involving ERCC2 Gene - Excision Repair Cross-Complementation Group 2 discovered through SciDEX knowledge graph analysis: