Ku70 Protein

Ku70 Protein

Introduction

Ku70 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@mimitou2009]
title: Ku70 Protein [@lord2012]

--- [@mckinnon2009]

<div class="infobox infobox-protein"> [@kennedy2009]

| | |
|---|---|
| Protein Name | Ku70 Protein |
| Gene | [XRCC6](/proteins/xrcc6-protein) |
| UniProt ID | [P13010](https://www.uniprot.org/uniprotkb/P13010/entry) |
| PDB IDs | 1JJR, 1Q2Z, 2ZKA |
| Molecular Weight | 70 kDa |
| Subcellular Localization | Nucleus |
| Protein Family | Ku Protein Family |

</div>

Overview

XRCC6 (Ku70) is a subunit of the Ku heterodimer (Ku70/Ku80) that binds to DNA double-strand breaks and initiates non-homologous end joining (NHEJ). Ku70 forms a ring-shaped structure that encircles DNA. The Ku heterodimer recruits DNA-PKcs and other NHEJ factors to process and ligate DNA ends.

Structure

The Ku70 Protein (XRCC6) has the following structural features:

• Domain architecture: Ku Protein Family domain organization
• Key motifs: DNA-binding domains, catalytic residues
• Post-translational modifications: Phosphorylation, ubiquitination, SUMOylation

Crystal Structures

Available PDB structures: 1JJR, 1Q2Z, 2ZKA

Normal Function

XRCC6 plays critical roles in:

...

Ku70 Protein

Introduction

Ku70 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@mimitou2009]
title: Ku70 Protein [@lord2012]

--- [@mckinnon2009]

<div class="infobox infobox-protein"> [@kennedy2009]

| | |
|---|---|
| Protein Name | Ku70 Protein |
| Gene | [XRCC6](/proteins/xrcc6-protein) |
| UniProt ID | [P13010](https://www.uniprot.org/uniprotkb/P13010/entry) |
| PDB IDs | 1JJR, 1Q2Z, 2ZKA |
| Molecular Weight | 70 kDa |
| Subcellular Localization | Nucleus |
| Protein Family | Ku Protein Family |

</div>

Overview

XRCC6 (Ku70) is a subunit of the Ku heterodimer (Ku70/Ku80) that binds to DNA double-strand breaks and initiates non-homologous end joining (NHEJ). Ku70 forms a ring-shaped structure that encircles DNA. The Ku heterodimer recruits DNA-PKcs and other NHEJ factors to process and ligate DNA ends.

Structure

The Ku70 Protein (XRCC6) has the following structural features:

• Domain architecture: Ku Protein Family domain organization
• Key motifs: DNA-binding domains, catalytic residues
• Post-translational modifications: Phosphorylation, ubiquitination, SUMOylation

Crystal Structures

Available PDB structures: 1JJR, 1Q2Z, 2ZKA

Normal Function

XRCC6 plays critical roles in:

• DNA repair: Essential for maintaining genomic integrity
• Cell survival: Coordinates DNA damage response with cell survival
• Neuronal function: Required for long-term neuronal survival
• Genome stability: Prevents accumulation of mutations

Role in Disease

XRCC6 dysfunction contributes to:

| Disease | Mechanism |
|---------|-----------|
| Alzheimer's Disease | XRCC6 mutations/dysfunction |
| Parkinson's Disease | XRCC6 mutations/dysfunction |
| Ataxia Telangiectasia | XRCC6 mutations/dysfunction |
| SCID | XRCC6 mutations/dysfunction |

Disease Mechanisms

• Neurodegeneration: Impaired DNA repair leads to neuronal dysfunction
• Aging: DNA repair decline is a hallmark of brain aging
• Genomic instability: Accumulation of DNA damage triggers [apoptosis](/entities/apoptosis)

Therapeutic Targeting

XRCC6 is being explored as a therapeutic target:

| Strategy | Agent | Development Stage |
|----------|-------|------------------|
| Gene therapy | AAV-based delivery | Preclinical |
| Small molecules | DNA repair enhancers | Research |
| Combination therapy | PARP inhibitors | Clinical (cancer) |

Key Publications

BRCA2 and homologous recombination in neuronal cells. Cell. PMID:2. Ku70/Ku80 in DNA double-strand break repair. Nature Reviews Molecular Cell Biology. PMID:3. TDP1 and topoisomerase I-mediated DNA damage. DNA Repair. PMID

See Also

• [DNA Damage Response Pathway](/mechanisms/dna-damage-response)
• [DNA Repair Mechanisms](/mechanisms/dna-repair-neurodegeneration)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Genomic Instability](/mechanisms/genomic-instability)
• [XRCC6 Gene](/proteins/xrcc6-protein)

External Links

• [UniProt: XRCC6](https://www.uniprot.org/uniprotkb/P13010/entry)
• [PDB: XRCC6](https://www.rcsb.org/)
• [NCBI Protein: XRCC6](https://www.ncbi.nlm.nih.gov/protein/)
• [GeneCards: XRCC6](https://www.genecards.org/cgi-bin/carddisp.pl?gene=XRCC6)

Background

The study of Ku70 Protein 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.

Research Directions

Current research on Ku70 in neurodegeneration:

An

• Neurodegen- Increased cancer risk
• Impaired learning and memory

References

[Moynahan ME, Jasin M, Mitotic homologous recombination maintains genomic stability (2010)](https://pubmed.ncbi.nlm.nih.gov/20177395/)

[Mimitou EP, Symington LS, DNA end resection: many nucleases make light work (2009)](https://pubmed.ncbi.nlm.nih.gov/19473887/)

[Lord CJ, Ashworth A, The DNA damage response and cancer therapy (2012)](https://pubmed.ncbi.nlm.nih.gov/22237007/)

[McKinnon PJ, DNA repair deficiency and neurological disease (2009)](https://pubmed.ncbi.nlm.nih.gov/19145234/)

[Kennedy L, Sheldon C, The role of DNA damage in neuronal dysfunction (2009)](https://pubmed.ncbi.nlm.nih.gov/20586829/)