title: Eukaryotic Rad50 functions as a rod-shaped dimer.
abstract: The 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.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Young Bong
authors.initials: YB
authors.lastname: Park
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Marcel
authors.initials: M
authors.lastname: Hohl
authors.affiliation: Laboratory of Chemical Biology, University of Wrocław, Wrocław, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Padjasek
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Jeong
authors.affiliation: Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Kyeong Sik
authors.initials: KS
authors.lastname: Jin
authors.affiliation: Laboratory of Chemical Biology, University of Wrocław, Wrocław, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Krężel
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: John H J
authors.initials: JH
authors.lastname: Petrini
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Yunje
authors.initials: Y
authors.lastname: Cho
mesh_terms: D017766:Acid Anhydride Hydrolases; D000595:Amino Acid Sequence; D059447:Cell Cycle Checkpoints; D018360:Crystallography, X-Ray; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008540:Meiosis; D008954:Models, Biological; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D000072417:Protein Domains; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015398:Signal Transduction; D012996:Solutions; D015032:Zinc / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D050505:Mutant Proteins; D012996:Solutions; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes; D015032:Zinc