Home LiteratureArticle Details
PMID: 18923082 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

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

Genes & development ·Vol. 22 ·No. 20 ·2008-10-15 ·Pages 2843-55

Xu D, Guo R, Sobeck A, Bachrati CZ, Yang J, Enomoto T, Brown GW, Hoatlin ME, Hickson ID, Wang W

Abstract

BLM, the helicase mutated in Bloom syndrome, associates with topoisomerase 3alpha, 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.

MeSH Terms
Amino Acid Sequence Animals Bloom Syndrome/metabolism Carrier Proteins/genetics,metabolism Cell Nucleus/metabolism Cells, Cultured Chickens DNA Damage DNA Helicases/physiology DNA Repair DNA Topoisomerases, Type I/physiology DNA, Cruciform DNA, Single-Stranded/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Genomic Instability HeLa Cells Humans Mitosis Molecular Sequence Data Nuclear Proteins/genetics,metabolism Oligonucleotides/chemistry,genetics,metabolism Phosphorylation Protein Folding RecQ Helicases Recombinant Proteins/genetics,isolation & purification,metabolism Recombination, Genetic Replication Protein A/genetics,metabolism Sequence Homology, Amino Acid Sister Chromatid Exchange
Chemicals
Carrier Proteins DNA, Cruciform DNA, Single-Stranded DNA-Binding Proteins Nuclear Proteins Oligonucleotides RMI1 protein, human RMI2 protein, human RPA1 protein, human Recombinant Proteins Replication Protein A Bloom syndrome protein DNA Helicases RecQ Helicases DNA Topoisomerases, Type I
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Xu Dongyi
Laboratory of Genetics, National Institute on Aging, National Institutes of Health, NIH Biomedical Research Center, Baltimore, Maryland 21224, USA.
Guo Rong
Sobeck Alexandra
Bachrati Csanad Z
Yang Jay
Enomoto Takemi
Brown Grant W
Hoatlin Maureen E
Hickson Ian D
Wang Weidong
References (42)
42 references, click to expand
  1. Mobile D-loops are a preferred substrate for the Bloom's syndrome helicase.
    Nucleic Acids Res. 2006;34(8):2269-79 PMID: 16670433
  2. BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates.
    Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4068-73 PMID: 16537486
  3. Topoisomerase IIIalpha and Bloom's helicase can resolve a mobile double Holliday junction substrate through convergent branch migration.
    Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11118-23 PMID: 16849422
  4. Bloom helicase and DNA topoisomerase IIIalpha are involved in the dissolution of sister chromatids.
    Mol Cell Biol. 2006 Aug;26(16):6299-307 PMID: 16880537
  5. MPS1-dependent mitotic BLM phosphorylation is important for chromosome stability.
    Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11485-90 PMID: 16864798
  6. The Bloom's syndrome helicase can promote the regression of a model replication fork.
    J Biol Chem. 2006 Aug 11;281(32):22839-46 PMID: 16766518
  7. A dynamic model for replication protein A (RPA) function in DNA processing pathways.
    Nucleic Acids Res. 2006;34(15):4126-37 PMID: 16935876
  8. DNA helicases required for homologous recombination and repair of damaged replication forks.
    Annu Rev Genet. 2006;40:279-306 PMID: 16856806
  9. Embryonic stem cells deficient for Brca2 or Blm exhibit divergent genotoxic profiles that support opposing activities during homologous recombination.
    Mutat Res. 2006 Dec 1;602(1-2):110-20 PMID: 16997331
  10. Binding and activation of DNA topoisomerase III by the Rmi1 subunit.
    J Biol Chem. 2007 Sep 28;282(39):28971-9 PMID: 17693398
  11. Functional interactions between BLM and XRCC3 in the cell.
    J Cell Biol. 2007 Oct 8;179(1):53-63 PMID: 17923529
  12. Holliday junction processing activity of the BLM-Topo IIIalpha-BLAP75 complex.
    J Biol Chem. 2007 Oct 26;282(43):31484-92 PMID: 17728255
  13. Genetic variant of the human homologous recombination-associated gene RMI1 (S455N) impacts the risk of AML/MDS and malignant melanoma.
    Cancer Lett. 2007 Dec 8;258(1):38-44 PMID: 17900800
  14. Novel pro- and anti-recombination activities of the Bloom's syndrome helicase.
    Genes Dev. 2007 Dec 1;21(23):3085-94 PMID: 18003860
  15. RecQ helicases: guardian angels of the DNA replication fork.
    Chromosoma. 2008 Jun;117(3):219-33 PMID: 18188578
  16. Functional role of BLAP75 in BLM-topoisomerase IIIalpha-dependent holliday junction processing.
    J Biol Chem. 2008 Jun 6;283(23):15701-8 PMID: 18390547
  17. BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome.
    Genes Dev. 2008 Oct 15;22(20):2856-68 PMID: 18923083
  18. A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75.
    J Biol Chem. 2006 May 19;281(20):13861-4 PMID: 16595695
  19. The Bloom's syndrome gene product interacts with topoisomerase III.
    J Biol Chem. 2000 Mar 31;275(13):9636-44 PMID: 10734115
  20. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.
    Genes Dev. 2000 Apr 15;14(8):927-39 PMID: 10783165
  21. The Bloom's syndrome gene product promotes branch migration of holliday junctions.
    Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6504-8 PMID: 10823897
  22. Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase.
    Oncogene. 2000 May 25;19(23):2731-8 PMID: 10851073
  23. Possible association of BLM in decreasing DNA double strand breaks during DNA replication.
    EMBO J. 2000 Jul 3;19(13):3428-35 PMID: 10880455
  24. Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity.
    J Biol Chem. 2000 Aug 4;275(31):23500-8 PMID: 10825162
  25. The role for zinc in replication protein A.
    J Biol Chem. 2000 Sep 1;275(35):27332-8 PMID: 10856290
  26. Binding and melting of D-loops by the Bloom syndrome helicase.
    Biochemistry. 2000 Nov 28;39(47):14617-25 PMID: 11087418
  27. Regulation and localization of the Bloom syndrome protein in response to DNA damage.
    J Cell Biol. 2001 Apr 16;153(2):367-80 PMID: 11309417
  28. Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51.
    J Biol Chem. 2001 Jun 1;276(22):19375-81 PMID: 11278509
  29. Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability.
    Hum Mol Genet. 2001 Jun 1;10(12):1287-98 PMID: 11406610
  30. Chromosomal instability in B-lymphoblasotoid cell lines from Werner and Bloom syndrome patients.
    Mutat Res. 2002 Sep 26;520(1-2):15-24 PMID: 12297140
  31. A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.
    Mol Cell Biol. 2003 May;23(10):3417-26 PMID: 12724401
  32. Nucleic acid recognition by OB-fold proteins.
    Annu Rev Biophys Biomol Struct. 2003;32:115-33 PMID: 12598368
  33. The Bloom's syndrome helicase suppresses crossing over during homologous recombination.
    Nature. 2003 Dec 18;426(6968):870-4 PMID: 14685245
  34. A manyfold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes.
    Proc Natl Acad Sci U S A. 1974 Nov;71(11):4508-12 PMID: 4140506
  35. Bloom syndrome: a mendelian prototype of somatic mutational disease.
    Medicine (Baltimore). 1993 Nov;72(6):393-406 PMID: 8231788
  36. Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM.
    EMBO J. 2005 Jan 26;24(2):418-27 PMID: 15616572
  37. ATR and ATM-dependent movement of BLM helicase during replication stress ensures optimal ATM activation and 53BP1 focus formation.
    Cell Cycle. 2004 Dec;3(12):1579-86 PMID: 15539948
  38. DNA binding by the substrate specificity (wedge) domain of RecG helicase suggests a role in processivity.
    J Biol Chem. 2005 Apr 8;280(14):13921-7 PMID: 15695524
  39. Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex.
    Mol Cell Biol. 2005 Jun;25(11):4476-87 PMID: 15899853
  40. BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity.
    EMBO J. 2005 Apr 6;24(7):1465-76 PMID: 15775963
  41. RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex.
    EMBO J. 2005 Jun 1;24(11):2024-33 PMID: 15889139
  42. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M.
    Nat Genet. 2005 Sep;37(9):958-63 PMID: 16116422
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1708608
Published
2008-10-15
Pages
2843-55
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2569887
Subset
IM
Grants
Intramural NIH HHS · Z01 AG000657 · United States
Corrections
CommentIn
PMID: 18923071
External Links
PubMed source DOI: 10.1101/gad.1708608 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2