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| XRCC5 (Ku80) Protein |
|---|
| Gene | [XRCC5](/genes/xrcc5) (X-ray Repair Cross-Complementing 5) |
| UniProt ID | [P13010](https://www.uniprot.org/uniprot/P13010) |
| PDB Structures | 1JJR, 1ZE4, 2R8Y |
| Molecular Weight | ~ 83 kDa |
| Subcellular Localization | Nucleus |
| Protein Family | Ku70/Ku80 heterodimer (NHEJ factors) |
is a protein encoded by the XRCC5 gene that ku80 is essential for non-homologous end joining (nhej), the predominant pathway for dna double-strand break repair in mammals:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Ku80 forms a heterodimeric complex with Ku70 to recognize and bind DNA double-strand breaks. The protein contains:
- N-terminal alpha/beta domain - DNA binding domain that encircles DNA ends
- Central beta-barrel - Forms the core of the DNA binding interface
- C-terminal arm - Flexible region mediating protein-protein interactions
- SAP domain - DNA binding and protein interaction motif
The Ku70/Ku80 dimer (Ku) wraps around DNA ends, forming a ring-like structure that slides onto DNA.
Ku80 is essential for non-homologous end joining (NHEJ), the predominant pathway for DNA double-strand break repair in mammals:
- DNA end recognition: Ku rapidly localizes to DSBs and encircles DNA ends
- Recruitment of NHEJ factors: Recruits DNA-PKcs, XRCC4, Ligase IV, and XLF
- DNA end processing: Facilitates minimal processing of broken ends
- Telomere maintenance: Essential for telomere length and integrity
In neurons:
- Critical for maintaining genomic stability
- Repair of spontaneous and induced DNA damage
- Neuronal activity-induced DNA damage repair
- Ku80 levels decline in AD brains
- Impaired NHEJ contributes to DNA damage accumulation
- Amyloid-beta reduces Ku80 expression and function
- Ku80 dysfunction in dopaminergic neurons
- Increased vulnerability to oxidative DNA damage
- Polymorphisms in XRCC5 associated with PD risk
- TDP-43 pathology disrupts Ku80 nuclear function
- Motor neurons show impaired NHEJ
- C9orf72-mediated DNA damage involves Ku80
- Mutant huntingtin impairs Ku80 recruitment to DNA damage
- NHEJ deficits contribute to neuronal dysfunction
- DNA-PK inhibitors: Target the NHEJ pathway in combination with Ku modulation
- Gene therapy: Expressing functional Ku80
- DNA damage response modulators: Enhance NHEJ efficiency