<!-- protein-page --> is a protein encoded by the [MRE11](/genes/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.
<!-- protein-page --> is a protein encoded by the [MRE11](/genes/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.
Structure
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.
Normal Function
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
[Unknown, Paull & Gellert, The 3' to 5' exonuclease activity of Mre11 facilitates DNA double-strand break repair (1998) (1998)](https://doi.org/10.1093/emboj/17.19.5738))
[Hopfner et al., Crystal structure of the Rad50-Mre11 DNA repair complex (2001) (2001)](https://doi.org/10.1093/emboj/20.22.6612))
[Lee et al., MRE11 deficiency in neurons leads to DNA damage and neurodegeneration (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/25849321/))
[Brosh et al., MRE11 and ATM in neurodegeneration (2019) (2019)](https://doi.org/10.1016/j.tibs.2019.06.007))
[Koh et al., MRE11 dysfunction in Alzheimer's disease (2021) (2021)](https://doi.org/10.1038/s41419-021-03567-1))