5gox

Structural highlights

Disease

[RAD50_HUMAN] Nijmegen breakage syndrome-like disorder;Hereditary breast and ovarian cancer syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

[RAD50_HUMAN] Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. 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 MRE11A to prevent nucleolytic degradation past a given point (PubMed:11741547, PubMed:9590181, PubMed:9705271, PubMed:9651580). 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).^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Zhu XD, Kuster B, Mann M, Petrini JH, de Lange T. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat Genet. 2000 Jul;25(3):347-52. PMID:10888888 doi:http://dx.doi.org/10.1038/77139
2. ↑ de Jager M, van Noort J, van Gent DC, Dekker C, Kanaar R, Wyman C. Human Rad50/Mre11 is a flexible complex that can tether DNA ends. Mol Cell. 2001 Nov;8(5):1129-35. PMID:11741547
3. ↑ Lee JH, Paull TT. Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science. 2004 Apr 2;304(5667):93-6. PMID:15064416 doi:http://dx.doi.org/10.1126/science.1091496
4. ↑ Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR 3rd, Hays L, Morgan WF, Petrini JH. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell. 1998 May 1;93(3):477-86. PMID:9590181
5. ↑ Paull TT, Gellert M. The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Mol Cell. 1998 Jun;1(7):969-79. PMID:9651580
6. ↑ Trujillo KM, Yuan SS, Lee EY, Sung P. Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95. J Biol Chem. 1998 Aug 21;273(34):21447-50. PMID:9705271