RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability

Dongyi Xu, Rong Guo, Alexandra Sobeck, Csanad Z. Bachrati, Jay Yang, Takemi Enomoto, Grant W. Brown, Maureen E. Hoatlin, Ian D. Hickson, Weidong Wang

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

BLM, the helicase mutated in Bloom syndrome, associates with topoisomerase 3α, RMI1 (RecQ-mediated genome instability), and RPA, to form a complex essential for the maintenance of genome stability. Here we report a novel component of the BLM complex, RMI2, which interacts with RMI1 through two oligonucleotide-binding (OB)-fold domains similar to those in RPA. The resulting complex, named RMI, differs from RPA in that it lacks obvious DNA-binding activity. Nevertheless, RMI stimulates the dissolution of a homologous recombination intermediate in vitro and is essential for the stability, localization, and function of the BLM complex in vivo. Notably, inactivation of RMI2 in chicken DT40 cells results in an increased level of sister chromatid exchange (SCE) - the hallmark feature of Bloom syndrome cells. Epistasis analysis revealed that RMI2 and BLM suppress SCE within the same pathway. A point mutation in the OB domain of RMI2 disrupts the association between BLM and the rest of the complex, and abrogates the ability of RMI2 to suppress elevated SCE. Our data suggest that multi-OB-fold complexes mediate two modes of BLM action: via RPA-mediated protein-DNA interaction, and via RMI-mediated protein-protein interactions.

Original languageEnglish (US)
Pages (from-to)2843-2855
Number of pages13
JournalGenes and Development
Volume22
Issue number20
DOIs
StatePublished - Oct 15 2008

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Keywords

  • BLAP75
  • BLM
  • Bloom syndrome
  • RMI1
  • RMI2
  • Topoisomerase 3α

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Xu, D., Guo, R., Sobeck, A., Bachrati, C. Z., Yang, J., Enomoto, T., Brown, G. W., Hoatlin, M. E., Hickson, I. D., & Wang, W. (2008). RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. Genes and Development, 22(20), 2843-2855. https://doi.org/10.1101/gad.1708608