ERCC1 — Excision Repair Cross-Complementation Group 1

ERCC1 — Excision Repair Cross-Complementation Group 1

Introduction

Ercc1 — Excision Repair Cross Complementation Group 1 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

The ERCC1 (Excision Repair Cross-Complementation Group 1) gene encodes a protein essential for DNA repair, particularly in the nucleotide excision repair (NER) pathway. It plays a critical role in maintaining genomic stability by repairing DNA lesions caused by environmental insults. [@wood2010]

Gene Information

ERCC1 — Excision Repair Cross-Complementation Group 1

Introduction

Ercc1 — Excision Repair Cross Complementation Group 1 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

The ERCC1 (Excision Repair Cross-Complementation Group 1) gene encodes a protein essential for DNA repair, particularly in the nucleotide excision repair (NER) pathway. It plays a critical role in maintaining genomic stability by repairing DNA lesions caused by environmental insults. [@wood2010]

Gene Information

<div class="infobox infobox-gene"> [@niedernhofer2004]
<table> [@mckay2000]
<tr><th>Gene Symbol</th><td>ERCC1</td></tr> [@hanawalt2002]
<tr><th>Full Name</th><td>Excision Repair Cross-Complementation Group 1</td></tr> [@sancar1996]
<tr><th>Chromosomal Location</th><td>19q13.32</td></tr> [@clarkson2003]
<tr><th>NCBI Gene ID</th><td>[2075](https://www.ncbi.nlm.nih.gov/gene/2075)</td></tr> [@friedberg1995]
<tr><th>OMIM</th><td>[126380](https://www.omim.org/entry/126380)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000112020</td></tr>
<tr><th>UniProt ID</th><td>[P49755](https://www.uniprot.org/uniprot/P49755)</td></tr>
<tr><th>Associated Diseases</th><td>Cockayne Syndrome, Xeroderma Pigmentosum, Fanconi Anemia</td></tr>
</table>
</div>

Function

ERCC1 functions as part of a heterodimer with XPF (ERCC4) to perform the critical incision step in nucleotide excision repair:

DNA Repair Mechanism

• Forms a tight heterodimer with XPF (ERCC1-XPF endonuclease)
• Recognizes and excises DNA lesions as part of NER pathway
• Makes the 5' incision adjacent to DNA damage
• Works together with XPA and replication protein A (RPA) to verify damage

DNA Damage Recognition

• Functions in both global genome NER (GG-NER) and transcription-coupled NER (TC-NER)
• Essential for removing UV-induced photoproducts
• Removes bulky chemical adducts and crosslinks
• Critical for repair of oxidative DNA damage

Cellular Processes

• Maintains genomic stability during DNA replication
• Facilitates DNA repair in actively transcribed genes
• Participates in interstrand crosslink repair
• Involved in double-strand break repair

Disease Associations

Cockayne Syndrome (CS)

• ERCC1 mutations can cause CS, a rare autosomal recessive disorder
• Features include:
• Severe growth retardation
• Neurological dysfunction
• Photosensitivity
• Premature aging
• Cognitive impairment

Xeroderma Pigmentosum (XP)

• Some ERCC1 mutations cause XP complementation group
• Extreme UV sensitivity
• High risk of skin cancers

Neurological Implications

• DNA repair deficiency leads to progressive neurodegeneration
• Accumulation of DNA damage in [neurons](/entities/neurons)
• Associated with [Alzheimer's](/diseases/alzheimers-disease) and [Parkinson's disease](/diseases/parkinsons-disease) pathogenesis
• May contribute to normal aging processes

Cancer

• Reduced ERCC1 expression is associated with poor prognosis in various cancers
• Important in chemotherapy response (platinum-based drugs)
• Polymorphisms affect cancer susceptibility

Expression

Brain Expression

• Expressed in all brain regions
• Higher expression in neurons compared to glia
• Upregulated in response to DNA damage
• Essential for neuronal survival

Cellular Localization

• Nuclear localization
• Associates with DNA repair foci after damage
• Forms nuclear foci during S-phase

Therapeutic Implications

Cancer Therapy

• ERCC1 expression predicts response to platinum chemotherapy
• Low ERCC1: better response to platinum agents
• Important biomarker for personalized cancer treatment

Neurodegeneration

• Enhancing DNA repair is a therapeutic target
• Gene therapy approaches being explored
• Small molecules to boost NER capacity under investigation

See Also

• [DNA Repair Mechanisms](/mechanisms/dna-repair-neurodegeneration)
• [Nucleotide Excision Repair](/mechanisms/nucleotide-excision-repair)
• [Cockayne Syndrome](/diseases/cockayne-syndrome)
• [DNA Damage and Neurodegeneration](/mechanisms/dna-damage-neurodegeneration)
• [XPF Gene](/genes/xpf)

Key Publications

Background

The study of Ercc1 — Excision Repair Cross Complementation Group 1 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

• [NCBI Gene: ERCC1](https://www.ncbi.nlm.nih.gov/gene/2075)
• [UniProt: ERCC1](https://www.uniprot.org/uniprot/P49755)
• [OMIM: ERCC1](https://www.omim.org/entry/126380)
• [Ensembl: ERCC1](https://www.ensembl.org/Homo_sapiens/ENSG00000112020)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving ERCC1 — Excision Repair Cross-Complementation Group 1 discovered through SciDEX knowledge graph analysis: