Association of MRE11 and NBS1 leads to nuclear localization of MRN complex

Stable Identifier
R-GGA-351412
Type
Reaction [binding]
Species
Gallus gallus
Compartment
nucleoplasm
ReviewStatus
5/5
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Association of MRE11 and NBS1 leads to nuclear localization of MRN complex
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MRE11-RAD50-NBS1 (MRN) is a ubiquitous and conserved nuclease complex involved in DNA break repair, cell cycle checkpoint control, meiotic recombination and telomere maintenance. MRE11 and RAD50 are homologs of proteins first identified in yeast by their effects on meiotic recombination (MRE11) and radiation sensitivity (RAD50). NBS1 (also known as nibrin) is mutated in the human genetic disease Nijmegen breakage syndrome. MRE11 and RAD50 form the catalytic core of the MRN complex; exonucleolytic and endonucleolytic activities are vested in MRE11; and DNA binding and ATPase activities are in RAD50. Chicken NBS1 is the regulatory subunit that interacts with MRE11 via its BRCA1 C terminus domain (aa 665-693) to govern nuclear localization and to generate a MRN-complex with a nuclease activity. The N-terminus region of NBS1, known as the forkhead-associated (FHA) domain, regulates nuclear foci formation of the multiprotein complex in response to DNA damage. NBS1 also responds to and regulates the ATM kinase, which is missing in the human genetic disease ataxia telangiectasia and is critical for cell cycle checkpoint signaling. Ectopic expression of NBS1, the regulatory subunit of MRN, accelerates gene conversion in the chicken B cell line DT40 suggesting that MRN promotes DNA cleavage and/or mutagenic repair of lesions initiated by activation induced deaminase, acting in the shared pathway of immunoglobulin gene diversification.
Literature References
PubMed ID Title Journal Year
15162012 Recombination repair pathway in the maintenance of chromosomal integrity against DNA interstrand crosslinks

Sasaki, MS, Takata, M, Sonoda, E, Tachibana, A, Takeda, S

Cytogenet Genome Res 2004
11062235 The forkhead-associated domain of NBS1 is essential for nuclear foci formation after irradiation but not essential for hRAD50[middle dot]hMRE11[middle dot]NBS1 complex DNA repair activity

Tauchi, H, Kobayashi, J, Morishima, K, Matsuura, S, Nakamura, A, Shiraishi, T, Ito, E, Masnada, D, Delia, D, Komatsu, K

J Biol Chem 2001
15937485 The MRE11-RAD50-NBS1 complex accelerates somatic hypermutation and gene conversion of immunoglobulin variable regions

Yabuki, M, Fujii, MM, Maizels, N

Nat Immunol 2005
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Authored
Saxena, A  (2008-07-07)
Reviewed
Borowiec, JA  (2009-04-24)
Created
Saxena, A  (2008-05-23)
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