5gox
Eukaryotic Rad50 Functions as A Rod-shaped Dimer
Structural highlights
DiseaseRAD50_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. FunctionRAD50_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] Publication Abstract from PubMedThe Rad50 hook interface is crucial for assembly and various functions of the Mre11 complex. Previous analyses suggested that Rad50 molecules interact within (intracomplex) or between (intercomplex) dimeric complexes. In this study, we determined the structure of the human Rad50 hook and coiled-coil domains. The data suggest that the predominant structure is the intracomplex, in which the two parallel coiled coils proximal to the hook form a rod shape, and that a novel interface within the coiled-coil domains of Rad50 stabilizes the interaction of Rad50 protomers in the dimeric assembly. In yeast, removal of the coiled-coil interface compromised Tel1 activation without affecting DNA repair, while simultaneous disruption of that interface and the hook phenocopied a null mutation. The results demonstrate that the hook and coiled-coil interfaces coordinately promote intracomplex assembly and define the intracomplex as the functional form of the Mre11 complex. Eukaryotic Rad50 functions as a rod-shaped dimer.,Park YB, Hohl M, Padjasek M, Jeong E, Jin KS, Krezel A, Petrini JH, Cho Y Nat Struct Mol Biol. 2017 Mar;24(3):248-257. doi: 10.1038/nsmb.3369. Epub 2017, Jan 30. PMID:28134932[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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