title: Structure and cellular roles of the RMI core complex from the bloom syndrome dissolvasome.
abstract: BLM, the protein product of the gene mutated in Bloom syndrome, is one of five human RecQ helicases. It functions to separate double Holliday junction DNA without genetic exchange as a component of the "dissolvasome," which also includes topoisomerase IIIα and the RMI (RecQ-mediated genome instability) subcomplex (RMI1 and RMI2). We describe the crystal structure of the RMI core complex, comprising RMI2 and the C-terminal OB domain of RMI1. The overall RMI core structure strongly resembles two-thirds of the trimerization core of the eukaryotic single-stranded DNA-binding protein, Replication Protein A. Immunoprecipitation experiments with RMI2 variants confirm key interactions that stabilize the RMI core interface. Disruption of this interface leads to a dramatic increase in cellular sister chromatid exchange events similar to that seen in BLM-deficient cells. The RMI core interface is therefore crucial for BLM dissolvasome assembly and may have additional cellular roles as a docking hub for other proteins.
authors.affiliation: Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, 550 Medical Science Center, 1300 University Avenue, Madison, WI 53706-1532, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Hoadley
authors.forename: Dongyi
authors.initials: D
authors.lastname: Xu
authors.forename: Yutong
authors.initials: Y
authors.lastname: Xue
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Satyshur
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
authors.forename: James L
authors.initials: JL
authors.lastname: Keck
mesh_terms: D001816:Bloom Syndrome / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry*; D011487:Protein Conformation; D053484:RecQ Helicases / Q000737:chemistry; D012854:Sister Chromatid Exchange
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C501527:RMI1 protein, human; C533196:RMI2 protein, human; C097151:Bloom syndrome protein; D053484:RecQ Helicases; D004264:DNA Topoisomerases, Type I
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