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 Hoatlin, Ian D. Hickson, Weidong Wang

Research output: Contribution to journalArticle

127 Citations (Scopus)

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

Fingerprint

Sister Chromatid Exchange
Genomic Instability
Bloom Syndrome
Oligonucleotides
Proteins
Homologous Recombination
DNA
Point Mutation
Chickens
Maintenance
Bloom syndrome protein

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., ... 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

RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. / Xu, Dongyi; Guo, Rong; Sobeck, Alexandra; Bachrati, Csanad Z.; Yang, Jay; Enomoto, Takemi; Brown, Grant W.; Hoatlin, Maureen; Hickson, Ian D.; Wang, Weidong.

In: Genes and Development, Vol. 22, No. 20, 15.10.2008, p. 2843-2855.

Research output: Contribution to journalArticle

Xu, D, Guo, R, Sobeck, A, Bachrati, CZ, Yang, J, Enomoto, T, Brown, GW, Hoatlin, M, Hickson, ID & Wang, W 2008, 'RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability', Genes and Development, vol. 22, no. 20, pp. 2843-2855. https://doi.org/10.1101/gad.1708608
Xu, Dongyi ; Guo, Rong ; Sobeck, Alexandra ; Bachrati, Csanad Z. ; Yang, Jay ; Enomoto, Takemi ; Brown, Grant W. ; Hoatlin, Maureen ; Hickson, Ian D. ; Wang, Weidong. / RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. In: Genes and Development. 2008 ; Vol. 22, No. 20. pp. 2843-2855.
@article{326d3159853d48e6b9e83c1eca8202f8,
title = "RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability",
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.",
keywords = "BLAP75, BLM, Bloom syndrome, RMI1, RMI2, Topoisomerase 3α",
author = "Dongyi Xu and Rong Guo and Alexandra Sobeck and Bachrati, {Csanad Z.} and Jay Yang and Takemi Enomoto and Brown, {Grant W.} and Maureen Hoatlin and Hickson, {Ian D.} and Weidong Wang",
year = "2008",
month = "10",
day = "15",
doi = "10.1101/gad.1708608",
language = "English (US)",
volume = "22",
pages = "2843--2855",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "20",

}

TY - JOUR

T1 - RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability

AU - Xu, Dongyi

AU - Guo, Rong

AU - Sobeck, Alexandra

AU - Bachrati, Csanad Z.

AU - Yang, Jay

AU - Enomoto, Takemi

AU - Brown, Grant W.

AU - Hoatlin, Maureen

AU - Hickson, Ian D.

AU - Wang, Weidong

PY - 2008/10/15

Y1 - 2008/10/15

N2 - 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.

AB - 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.

KW - BLAP75

KW - BLM

KW - Bloom syndrome

KW - RMI1

KW - RMI2

KW - Topoisomerase 3α

UR - http://www.scopus.com/inward/record.url?scp=54349099705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54349099705&partnerID=8YFLogxK

U2 - 10.1101/gad.1708608

DO - 10.1101/gad.1708608

M3 - Article

C2 - 18923082

AN - SCOPUS:54349099705

VL - 22

SP - 2843

EP - 2855

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 20

ER -