MRE11

This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

MRE11 Homolog, Double Strand Break Repair Nuclease

Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289).

The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11 (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289).

RAD50 may be required to bind DNA ends and hold them in close proximity (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289).

This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11 to prevent nucleolytic degradation past a given point (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289, PubMed:30612738).

The complex may also be required for DNA damage signaling via activation of the ATM kinase (PubMed:15064416).

In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888).

Cell population proliferation Source: Ensembl
Cellular response to DNA damage stimulus Source: UniProtKB
DNA double-strand break processing Source: Reactome
DNA duplex unwinding Source: BHF-UCL
DNA recombination Source: ProtInc
DNA repair Source: ProtInc
DNA strand resection involved in replication fork processing Source: UniProtKB
Double-strand break repair Source: ProtInc
Double-strand break repair via homologous recombination Source: UniProtKB
Double-strand break repair via nonhomologous end joining Source: CACAO
Homologous chromosome pairing at meiosis Source: Ensembl
Homologous recombination Source: ComplexPortal
Meiotic DNA double-strand break formation Source: GO_Central
Mitochondrial double-strand break repair via homologous recombination Source: GO_Central
Mitotic G2/M transition checkpoint Source: ComplexPortal
Mitotic G2 DNA damage checkpoint signaling Source: GO_Central
Mitotic intra-S DNA damage checkpoint signaling Source: GO_Central
Negative regulation of apoptotic process Source: BHF-UCL
Positive regulation of kinase activity Source: BHF-UCL
Positive regulation of protein autophosphorylation Source: BHF-UCL
Positive regulation of telomere maintenance Source: BHF-UCL
Reciprocal meiotic recombination Source: ProtInc
Regulation of mitotic recombination Source: ProtInc
Sister chromatid cohesion Source: BHF-UCL
Telomere maintenance Source: GO_Central
Telomere maintenance via telomerase Source: ProtInc
Telomeric 3' overhang formation Source: BHF-UCL

Nucleus
Other locations
telomere
Chromosome
Note: Localizes to discrete nuclear foci after treatment with genotoxic agents.

Ataxia-telangiectasia-like disorder 1 (ATLD1):
A rare disorder characterized by progressive cerebellar ataxia, dysarthria, abnormal eye movements, and absence of telangiectasia. ATLD patients show normal levels of total IgG, IgA and IgM, although there may be reduced levels of specific functional antibodies. At the cellular level, ATLD exhibits hypersensitivity to ionizing radiation and radioresistant DNA synthesis.
Defects in MRE11 can be a cause of nephronophthisis-related ciliopathies (NPHP-RC), a group of recessive diseases that affect kidney, retina and brain. A homozygous truncating mutation MRE11 has been found in patients with cerebellar vermis hypoplasia, ataxia and dysarthria.

Ubiquitinated following DNA damage. Ubiquitination triggers interaction with UBQLN4, leading to MRE11 removal from chromatin and degradation by the proteasome.