ERCC6 — Excision Repair Cross-Complementation Group 6

ERCC6 — Excision Repair Cross-Complementation Group 6

Introduction

Ercc6 — Excision Repair Cross Complementation Group 6 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 ERCC6 (Excision Repair Cross-Complementation Group 6) gene, also known as Cockayne Syndrome B (CSB), encodes a protein critical for transcription-coupled nucleotide excision repair (TC-NER). Mutations in ERCC6 cause Cockayne syndrome, a severe disorder characterized by premature aging and neurodegeneration. [@troelstra1992]

Gene Information

<div class="infobox infobox-gene"> [@brooks2008]
<table> [@citterio2000]
<tr><th>Gene Symbol</th><td>ERCC6</td></tr> [@nardo2019]
<tr><th>Full Name</th><td>Excision Repair Cross-Complementation Group 6 (Cockayne Syndrome B)</td></tr> [@lans2019]
<tr><th>Chromosomal Location</th><td>10q11.23</td></tr> [@maynard2015]
<tr><th>NCBI Gene ID</th><td>[2073](https://www.ncbi.nlm.nih.gov/gene/2073)</td></tr> [@weissman2007]
<tr><th>OMIM</th><td>[133540](https://www.omim.org/entry/133540)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000225830</td></tr>
<tr><th>UniProt ID</th><td>[Q03468](https://www.uniprot.org/uniprot/Q03468)</td></tr>
<tr><th>Associated Diseases</th><td>Cockayne Syndrome Type II, UV-Sensitive Syndrome</td></tr>
</table>
</div>

Function

The ERCC6/CSB protein is a key regulator of transcription-coupled DNA repair:

ERCC6 — Excision Repair Cross-Complementation Group 6

Introduction

Ercc6 — Excision Repair Cross Complementation Group 6 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 ERCC6 (Excision Repair Cross-Complementation Group 6) gene, also known as Cockayne Syndrome B (CSB), encodes a protein critical for transcription-coupled nucleotide excision repair (TC-NER). Mutations in ERCC6 cause Cockayne syndrome, a severe disorder characterized by premature aging and neurodegeneration. [@troelstra1992]

Gene Information

<div class="infobox infobox-gene"> [@brooks2008]
<table> [@citterio2000]
<tr><th>Gene Symbol</th><td>ERCC6</td></tr> [@nardo2019]
<tr><th>Full Name</th><td>Excision Repair Cross-Complementation Group 6 (Cockayne Syndrome B)</td></tr> [@lans2019]
<tr><th>Chromosomal Location</th><td>10q11.23</td></tr> [@maynard2015]
<tr><th>NCBI Gene ID</th><td>[2073](https://www.ncbi.nlm.nih.gov/gene/2073)</td></tr> [@weissman2007]
<tr><th>OMIM</th><td>[133540](https://www.omim.org/entry/133540)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000225830</td></tr>
<tr><th>UniProt ID</th><td>[Q03468](https://www.uniprot.org/uniprot/Q03468)</td></tr>
<tr><th>Associated Diseases</th><td>Cockayne Syndrome Type II, UV-Sensitive Syndrome</td></tr>
</table>
</div>

Function

The ERCC6/CSB protein is a key regulator of transcription-coupled DNA repair:

Transcription-Coupled Repair (TC-NER)

• Initiates TC-NER when RNA polymerase II stalls at DNA lesions
• Recruits repair machinery to actively transcribed genes
• Removes blocking lesions from the transcribed strand
• Essential for maintaining transcriptional fidelity

Chromatin Remodeling

• Possesses ATP-dependent chromatin remodeling activity
• Facilitates access of repair proteins to DNA
• Modifies nucleosome structure around damage sites
• Works with [histone modifications](/entities/histone-modifications) to promote repair

Transcriptional Regulation

• Functions as a transcriptional coactivator
• Interacts with RNA polymerase II and general transcription factors
• Modulates gene expression in response to DNA damage
• Involved in basal transcription machinery

Mitochondrial Function

• Important for mitochondrial DNA repair
• Maintains mitochondrial genome integrity
• Affects mitochondrial biogenesis

Disease Associations

Cockayne Syndrome (CS)

• Severe growth failure after birth
• Neurological dysfunction and developmental delay
• Progressive motor impairment
• Photosensitivity (without pigmentation)
• Premature aging phenotype
• Cachexia
• Short lifespan (typically 5-7 years)

UV-Sensitive Syndrome (UVSS)

• Milder phenotype with photosensitivity
• Minimal neurological involvement
• Similar cellular repair defects

Neurological Implications

• Progressive neurodegeneration is hallmark
• Neuronal loss in cerebellum and brainstem
• Demyelination and calcifications
• Mouse models show accelerated aging
• Implications for sporadic neurodegeneration

Research Implications

• Model for understanding aging processes
• Insights into DNA repair and neurodegeneration
• Potential therapeutic targets

Expression

Brain Expression

• High expression in [neurons](/entities/neurons) of [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum
• Expressed in glial cells
• Upregulated in response to DNA damage
• Essential for neuronal homeostasis

Cellular Localization

• Nuclear localization
• Associates with transcription machinery
• Found at sites of DNA damage
• Some mitochondrial localization

Therapeutic Implications

Current Approaches

• No effective treatment available
• Supportive care for symptoms
• Gene therapy being explored
• Small molecule screening for modulators

Research Directions

• Enhancing DNA repair capacity
• Antioxidant therapies
• Mitochondrial function preservation
• Gene replacement strategies

See Also

• [DNA Repair Mechanisms](/mechanisms/dna-repair-neurodegeneration)mechanisms/dna-repair-neurodegeneration)
• [Transcription-Coupled Repair](/mechanisms/transcription-coupled-repair)
• [Cockayne Syndrome](/diseases/cockayne-syndrome)
• [DNA Damage and Neurodegeneration](/mechanisms/dna-damage-neurodegeneration)
• [ERCC8 Gene](/genes/ercc8)
• [Premature Aging](/mechanisms/premature-aging)

Key Publications

Background

The study of Ercc6 — Excision Repair Cross Complementation Group 6 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: ERCC6](https://www.ncbi.nlm.nih.gov/gene/2073)
• [UniProt: ERCC6/CSB](https://www.uniprot.org/uniprot/Q03468)
• [OMIM: ERCC6](https://www.omim.org/entry/133540)
• [Ensembl: ERCC6](https://www.ensembl.org/Homo_sapiens/ENSG00000225830)

References