A multiprotein nuclear complex connects fanconi anemia and bloom syndrome

Amom Ruhikanta Meetei, Salvatore Sechi, Michael Wallisch, Dafeng Yang, Mary K. Young, Hans Joenje, Maureen Hoatlin, Weidong Wang

Research output: Contribution to journalArticle

273 Citations (Scopus)

Abstract

Bloom syndrome (BS) is a genetic disorder associated with dwarfism, immunodeficiency, reduced fertility, and an elevated risk of cancer. To investigate the mechanism of this disease, we isolated from human HeLa extracts three complexes containing the helicase defective in BS, BLM. Interestingly, one of the complexes, termed BRAFT, also contains five of the Fanconi anemia (FA) complementation group proteins (FA proteins). FA resembles BS in genomic instability and cancer predisposition, but most of its gene products have no known biochemical activity, and the molecular pathogenesis of the disease is poorly understood. BRAFT displays a DNA-unwinding activity, which requires the presence of BLM because complexes isolated from BLM-deficient cells lack such an activity. The complex also contains topoisomerase IIIα and replication protein A, proteins that are known to interact with BLM and could facilitate unwinding of DNA. We show that BLM complexes isolated from an FA cell line have a lower molecular mass. Our study provides the first biochemical characterization of a multiprotein FA complex and suggests a connection between the BLM and FA pathways of genomic maintenance. The findings that FA proteins are part of a DNA-unwinding complex imply that FA proteins may participate in DNA repair.

Original languageEnglish (US)
Pages (from-to)3417-3426
Number of pages10
JournalMolecular and Cellular Biology
Volume23
Issue number10
DOIs
StatePublished - May 2003

Fingerprint

Bloom Syndrome
Fanconi Syndrome
Fanconi Anemia
Multiprotein Complexes
Fanconi Anemia Complementation Group Proteins
DNA
Replication Protein A
Dwarfism
Inborn Genetic Diseases
Genomic Instability
Complex Mixtures
DNA Repair
Fertility
Neoplasms
Maintenance
Cell Line
Genes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Meetei, A. R., Sechi, S., Wallisch, M., Yang, D., Young, M. K., Joenje, H., ... Wang, W. (2003). A multiprotein nuclear complex connects fanconi anemia and bloom syndrome. Molecular and Cellular Biology, 23(10), 3417-3426. https://doi.org/10.1128/MCB.23.10.3417-3426.2003

A multiprotein nuclear complex connects fanconi anemia and bloom syndrome. / Meetei, Amom Ruhikanta; Sechi, Salvatore; Wallisch, Michael; Yang, Dafeng; Young, Mary K.; Joenje, Hans; Hoatlin, Maureen; Wang, Weidong.

In: Molecular and Cellular Biology, Vol. 23, No. 10, 05.2003, p. 3417-3426.

Research output: Contribution to journalArticle

Meetei, AR, Sechi, S, Wallisch, M, Yang, D, Young, MK, Joenje, H, Hoatlin, M & Wang, W 2003, 'A multiprotein nuclear complex connects fanconi anemia and bloom syndrome', Molecular and Cellular Biology, vol. 23, no. 10, pp. 3417-3426. https://doi.org/10.1128/MCB.23.10.3417-3426.2003
Meetei, Amom Ruhikanta ; Sechi, Salvatore ; Wallisch, Michael ; Yang, Dafeng ; Young, Mary K. ; Joenje, Hans ; Hoatlin, Maureen ; Wang, Weidong. / A multiprotein nuclear complex connects fanconi anemia and bloom syndrome. In: Molecular and Cellular Biology. 2003 ; Vol. 23, No. 10. pp. 3417-3426.
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