Structure and Cellular Roles of the RMI Core Complex from the Bloom Syndrome Dissolvasome

Journal Article · Thu Nov 11 04:00:00 EST 2010 · Structure

DOI:https://doi.org/10.1016/j.str.2010.06.009· OSTI ID:1002748

Hoadley, Kelly A; Xu, Dongyi; Xue, Yutong; Satyshur, Kenneth A; Wang, Weidong; Keck, James L ^[1]

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1. NIH

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 III{alpha} 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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002748
• Journal Information: Structure, Journal Name: Structure Journal Issue: (9) ; 09, 2010 Vol. 18
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
DNA
GENES
GENETICS
INSTABILITY
PROTEINS
SISTER CHROMATID EXCHANGES