MRN complex

The MRN complex (MRX complex in yeast) is a protein complex consisting of Mre11, Rad50 and Nbs1 (also known as Nibrin [1] in humans and as Xrs2 in yeast). In eukaryotes, the MRN/X complex plays an important role in the initial processing of double-strand DNA breaks prior to repair by homologous recombination or non-homologous end joining. The MRN complex binds avidly to double-strand breaks both in vitro and in vivo and may serve to tether broken ends prior to repair by non-homologous end joining or to initiate resection prior to repair by homologous recombination. The MRN complex also participates in activating the checkpoint kinase ATM in response to DNA damage.[2][3] Production of short single-strand oligonucleotides by Mre11 endonuclease activity has been implicated in ATM activation by the MRN complex.[4]

Evolutionary ancestry and biologic function

The MRN complex has been mainly studied in eukaryotes. However, recent work shows that two of the three protein components of this complex, Mre11 and Rad50, are also conserved in extant prokaryotic archaea.[5] This finding suggests that key components of the eukaryotic MRN complex are derived by evolutionary descent from the archaea. In the archaeon Sulfolobus acidocaldarius, the Mre11 protein interacts with the Rad50 protein and appears to have an active role in the repair of DNA damages experimentally introduced by gamma radiation.[6] Similarly, during meiosis in the eukaryotic protist Tetrahymena Mre11 is required for repair of DNA damages, in this case double-strand breaks,[7] by a process that likely involves homologous recombination.

Role in human disease

Mutations in the human Nbs1 subunit of the MRN complex have been implicated in the rare genetic disorder Nijmegen Breakage Syndrome.[8]

See also

References

  1. ↑ "Atlas of Genetics and Cytogenetics in Oncology and Haematology - NBS1". Retrieved 2008-02-12.
  2. ↑ Lee, JH; Paull, TT (Apr 2, 2004). "Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex.". Science 304 (5667): 93–6. doi:10.1126/science.1091496. PMID 15064416.
  3. ↑ Lee, JH; Paull, TT (Apr 22, 2005). "ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex.". Science 308 (5721): 551–4. doi:10.1126/science.1108297. PMID 15790808.
  4. ↑ Jazayeri A, Balestrini A, Garner E, Haber JE, Costanzo V (2008). "Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity" (PDF). The EMBO Journal 27 (14): 1953–1962. doi:10.1038/emboj.2008.128. PMC 2453060. PMID 18596698.
  5. ↑ White MF. (2011). Homologous recombination in the archaea: the means justify the ends. Biochem Soc Trans 39(1):15-9. doi: 10.1042/BST0390015. Review. PMID 21265740
  6. ↑ Quaiser A, Constantinesco F, White MF, Forterre P, Elie C. (2008). The Mre11 protein interacts with both Rad50 and the HerA bipolar helicase and is recruited to DNA following gamma irradiation in the archaeon Sulfolobus acidocaldarius. BMC Mol Biol 9:25. doi: 10.1186/1471-2199-9-25. PMID 18294364
  7. ↑ Lukaszewicz A, Howard-Till RA, Novatchkova M, Mochizuki K, Loidl J. (2010). MRE11 and COM1/SAE2 are required for double-strand break repair and efficient chromosome pairing during meiosis of the protist Tetrahymena. Chromosoma 119(5):505-18. doi: 10.1007/s00412-010-0274-9. PMID 20422424
  8. ↑ "eMedicine - Nijmegen Breakage Syndrome". Retrieved 2008-02-12.
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