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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.
AuthorsKelly A Hoadley, Dongyi Xu, Yutong Xue, Kenneth A Satyshur, Weidong Wang, James L Keck
JournalStructure (London, England : 1993) (Structure) Vol. 18 Issue 9 Pg. 1149-58 (Sep 08 2010) ISSN: 1878-4186 [Electronic] United States
PMID20826341 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
CopyrightCopyright © 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
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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