9bi5

Structural highlights

Function

RAD50_YEAST 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:26896444, PubMed:28134932). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (By similarity). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of TEL1/ATM and ATR upon DNA damage (PubMed:26896444, PubMed:28134932). The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (By similarity). Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11 (PubMed:26896444). RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form (By similarity). The MRN complex is also required for the processing of R-loops (PubMed:31537797).[UniProtKB:Q92878][UniProtKB:Q9X1X1]^{[1] [2] [3]}

References

1. ↑ Seifert FU, Lammens K, Stoehr G, Kessler B, Hopfner KP. Structural mechanism of ATP-dependent DNA binding and DNA end bridging by eukaryotic Rad50. EMBO J. 2016 Feb 19. pii: e201592934. PMID:26896444 doi:http://dx.doi.org/10.15252/embj.201592934
2. ↑ Park YB, Hohl M, Padjasek M, Jeong E, Jin KS, Krezel A, Petrini JH, Cho Y. Eukaryotic Rad50 functions as a rod-shaped dimer. Nat Struct Mol Biol. 2017 Mar;24(3):248-257. doi: 10.1038/nsmb.3369. Epub 2017, Jan 30. PMID:28134932 doi:http://dx.doi.org/10.1038/nsmb.3369
3. ↑ Chang EY, Tsai S, Aristizabal MJ, Wells JP, Coulombe Y, Busatto FF, Chan YA, Kumar A, Dan Zhu Y, Wang AY, Fournier LA, Hieter P, Kobor MS, Masson JY, Stirling PC. MRE11-RAD50-NBS1 promotes Fanconi Anemia R-loop suppression at transcription-replication conflicts. Nat Commun. 2019 Sep 19;10(1):4265. PMID:31537797 doi:10.1038/s41467-019-12271-w