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| MRE11 Protein |
|---|
| Gene | [MRE11](/genes/mre11) (Meiotic Recombination 11 Homolog) |
| UniProt ID | [P49736](https://www.uniprot.org/uniprot/P49736) |
| PDB Structures | 1L8K, 3T8I, 5D5W |
| Molecular Weight | ~ 81 kDa |
| Subcellular Localization | Nucleus (MRN complex) |
| Protein Family | MRE11/RAD50/NBS1 (MRN) complex |
is a protein encoded by the MRE11 gene that mre11 is central to the dna damage response (ddr) network:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
MRE11 forms a key component of the MRN complex (MRE11-RAD50-NBS1) essential for DNA double-strand break (DSB) sensing and repair. The protein contains:
- Nuclease domain - Contains conserved phosphoesterase motif (HD domain) with endonuclease and 3'-to-5' exonuclease activity
- DNA binding domain - C-terminal domain that binds double-stranded DNA
- Rad50 interaction domain - Mediates heterotrimeric complex formation with RAD50
- NBS1 interaction site - C-terminal region for NBS1 binding
The MRE11 dimer wraps around DNA ends, with the nuclease domain processing broken ends for subsequent repair.
MRE11 is central to the DNA damage response (DDR) network:
- DSB detection: MRN complex rapidly localizes to DNA double-strand breaks
- DNA end processing: MRE11's nuclease activity resects DNA ends for homologous recombination
- ATM activation: MRN recruits and activates the ATM kinase
- Cell cycle checkpoint: NBS1-MRE11-ATM signaling triggers cell cycle arrest
In neurons, MRE11 maintains genomic integrity during:
- Neurogenesis
- DNA repair in post-mitotic neurons
- Response to oxidative DNA damage
- MRE11 deficiency accelerates cognitive decline in AD mouse models
- Impaired MRN complex function leads to increased DNA damage accumulation
- MRE11 mislocalization observed in AD brains with tau pathology
- MRE11 dysfunction contributes to dopaminergic neuron vulnerability
- Mitochondrial DNA damage in PD involves altered MRE11 activity
- Ataxia-telangiectasia-like disorder (ATLD) caused by MRE11 mutations shows neurodegeneration
- TDP-43 pathology disrupts MRE11 nuclear localization
- Impaired DNA repair in motor neurons with MRE11 dysfunction
- C9orf72 repeats cause DNA damage that involves MRE11
- MRE11 activity modulated by mutant huntingtin protein
- DNA repair deficits contribute to neuronal dysfunction
- MRE11 inhibitors: Being developed as radiosensitizers for cancer therapy
- ATM/MRE11 axis: Combined targeting for neurodegenerative diseases
- Gene therapy: Restoring MRE11 function in deficiency states
- PARP inhibitors: Synthetic lethality approaches in MRE11-deficient contexts