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.
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Authors | Kelly A Hoadley, Dongyi Xu, Yutong Xue, Kenneth A Satyshur, Weidong Wang, James L Keck |
Journal | Structure (London, England : 1993)
(Structure)
Vol. 18
Issue 9
Pg. 1149-58
(Sep 08 2010)
ISSN: 1878-4186 [Electronic] United States |
PMID | 20826341
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
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Copyright | Copyright © 2010 Elsevier Ltd. All rights reserved. |
Chemical References |
- Carrier Proteins
- DNA-Binding Proteins
- Nuclear Proteins
- RMI1 protein, human
- RMI2 protein, human
- Bloom syndrome protein
- RecQ Helicases
- DNA Topoisomerases, Type I
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Topics |
- Bloom Syndrome
(metabolism)
- Carrier Proteins
(chemistry)
- DNA Topoisomerases, Type I
(chemistry, metabolism)
- DNA-Binding Proteins
(chemistry)
- HeLa Cells
- Humans
- Models, Molecular
- Mutation
- Nuclear Proteins
(chemistry)
- Protein Conformation
- RecQ Helicases
(chemistry)
- Sister Chromatid Exchange
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