Description
Mre11 (double-strand break repair protein MRE11A) is an important component of
MRN/X complex (Mre11,
Rad50, and
Nbs1/Xrs2), playing a central role in
double-strand break (DSB) repair, DNA recombination, telomere integrity maintenance, meiotic cell division, and viral infection. Mre11 and Rad50 comprise the catalytic component of the MRN complex with Rad50 involved in ATP hydrolysis and Mre11 functioning as a nuclease having both single-strand endonuclease and double-strand-specific 3'-5' exonuclease activity (1). The MRN complex is also involved in DNA damage signaling via activation of
ATM kinase and in telomeres, where it may modulate t-loop formation (2). In addition, Mre11 is a component of the BASC complex (
BRCA1,
MSH2,
MSH6,
MLH1, ATM,
BLM, RAD50, MRE11A and NBN) and interacts with
DCLRE1C/Artemis as well as
DCLRE1B/Apollo (3).
The MRN assembles as a hetero-hexamer consisting of 2 RAD50 subunits, 2 MRE11 nucleases, and 2 NBS1 subunits, specific to eukaryotes. Mre11 is highly conserved with the N-terminal region of the human protein sharing approximately 50% amino acid sequence identity with the yeast ortholog. Human Mre11 has 3 known isoforms with the predominant isoform having a theoretical molecular weight of 80.6kDa. This nuclear localized protein has high expression in proliferating tissues. Defects in Mre11 can lead to genomic instability, telomere shortening, aberrant meiosis, hypersensitivity to DNA damage, and ataxia telangiectasia-like disorder (ATLD). MRN expression has been associated with the prognosis of
cancer and MRN mutants have been linked to cancer susceptibility in ovarian cancer and glioma (4, 5).
References
1. Paull TT. (2018) 20 Years of Mre11 Biology: No End in Sight. Mol Cell. 71(3):419-427. PMID: 30057197
2. Syed A, Tainer JA. (2018) The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair. Annu Rev Biochem. 87:263-294. PMID: 29709199
3. Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J. (2000) BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. 14(8):927-39. PMID: 10783165
4. Kim JH, Grosbart M, Anand R, Wyman C, Cejka P, Petrini JHJ. (2017) The Mre11-Nbs1 Interface Is Essential for Viability and Tumor Suppression. Cell Rep. 18(2):496-507. PMID: 28076792
5. Bian L, Meng Y, Zhang M, Li D. (2019) MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment. Mol Cancer. 18(1):169. PMID: 31767017
Bioinformatics
| Entrez |
Mouse
Human
Rat
|
| Uniprot |
Human
Human
Human
|
| Product By Gene ID |
4361 |
| Alternate Names |
- ATLDmeiotic recombination (S. cerevisiae) 11 homolog A
- AT-like disease
- DNA recombination and repair protein
- double-strand break repair protein MRE11A
- endo/exonuclease Mre11
- HNGS1
- Meiotic recombination 11 homolog 1
- Meiotic recombination 11 homolog A
- MRE11 homolog 1
- MRE11 homolog A
- MRE11 meiotic recombination 11 homolog A (S. cerevisiae)
- MRE11B
|
