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| XRCC3 Protein |
|---|
| Gene | [XRCC3](/genes/xrcc3) (X-ray Repair Cross-Complementing 3) |
| UniProt ID | [Q9UQE5](https://www.uniprot.org/uniprot/Q9UQE5) |
| PDB Structures | 1O8C, 2J8M |
| Molecular Weight | ~ 38 kDa |
| Subcellular Localization | Nucleus |
| Protein Family | RecA/RAD51 family (RecA-like ATPases) |
is a protein encoded by the XRCC3 gene that xrcc3 is essential for error-free homologous recombination:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
XRCC3 is a member of the RecA/RAD51 family of proteins involved in homologous recombination (HR) repair. Key structural features:
- RAD51 binding domain - Forms complexes with RAD51 and RAD51C
- ATPase domain - Binds and hydrolyzes ATP for filament formation
- DNA binding domain - Binds single-stranded and double-stranded DNA
- C-terminal domain - Mediates protein-protein interactions in the HR complex
XRCC3 functions as a RAD51 paralog, forming the RAD51C-XRCC3 (CX3) complex that stabilizes RAD51 filaments.
XRCC3 is essential for error-free homologous recombination:
- RAD51 filament stabilization: XRCC3 helps nucleate and stabilize RAD51 filaments on ssDNA
- DNA damage response: Mediates resistance to ionizing radiation and DNA crosslinking agents
- Sister chromatid exchange: Promotes proper sister chromatid exchange during repair
- Cell cycle checkpoint: ATR-dependent phosphorylation regulates XRCC3 activity
In neurons:
- Maintains genomic stability in post-mitotic neurons
- Facilitates repair of oxidative DNA damage
- Supports neuronal DNA repair during aging
- XRCC3 deficiency associated with increased DNA damage in AD brains
- Impaired homologous recombination in neurons with amyloid pathology
- Polymorphisms in XRCC3 linked to AD risk
- XRCC3 variants associated with PD susceptibility
- Dopaminergic neurons show increased vulnerability with XRCC3 dysfunction
- Mitochondrial DNA repair involvement through alternative pathways
- Motor neurons with TDP-43 pathology show XRCC3 mislocalization
- Impaired DNA repair contributes to ALS progression
- C9orf72-mediated DNA damage involves XRCC3
- Mutant huntingtin interferes with XRCC3 function
- DNA repair deficits in HD neurons linked to XRCC3
- RAD51/XRCC3 modulators: Being developed for cancer therapy
- DNA damage response enhancers: To boost neuronal DNA repair
- Gene therapy approaches: Restoring XRCC3 function