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The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia

Nature Genetics volume 37, pages 931–933 (2005)Cite this article

An Addendum to this article was published on 01 November 2005

Abstract

Seven Fanconi anemia–associated proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG and FANCL) form a nuclear Fanconi anemia core complex that activates the monoubiquitination of FANCD2, targeting FANCD2 to BRCA1-containing nuclear foci. Cells from individuals with Fanconi anemia of complementation groups D1 and J (FA-D1 and FA-J) have normal FANCD2 ubiquitination. Using genetic mapping, mutation identification and western-blot data, we identify the defective protein in FA-J cells as BRIP1 (also called BACH1), a DNA helicase that is a binding partner of the breast cancer tumor suppressor BRCA1.

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Figure 1: BRIP1 is defective in Fanconi anemia.

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Acknowledgements

We thank the affected individuals and their families for providing tissue samples for these studies; the many physicians who referred their patients to the IFAR and helped in sending the tissue samples for their contributions; A. Dawson, B. Chodirker and G. Graham for providing samples from the Inuit families, which were instrumental to the success of the mapping experiments; S. Cantor for the monopool BRIP1 antibody; Myriad Genetic Laboratories for sequencing BRCA2 in IFAR samples; F. Lach, S. Arama, B. Zhang and Y. Flit for technical assistance; and J. Morales, C. Zhao and J. Lowe for advice. This work was supported in part by grants from the US National Institutes of Health (to A.D.A. and to J.P.), by the Joel and Joan Smilow Initiative (J.P.); by Kinderkrebsklinik Duesseldorf e. V. (H.H.); by CIEMAT and the Marcelino Botin Foundation (P.R.); by the Schroeder-Kurth Fund and the Deutsche Fanconi-Anamie-Hilfe (K.N., R.K. and D.S.); and by the Fanconi Anemia Research Fund (H.H.).

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Author notes

  1. Paula Rio

    Present address: CIEMAT/Marcelino Botin Foundation, Madrid, Spain

  2. Detlev Schindler, Helmut Hanenberg and Arleen D Auerbach: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory for Human Genetics & Hematology, The Rockefeller University, New York, New York, USA

    Orna Levran, Rashida T Henry, Kelly L Milton, Sat Dev Batish & Arleen D Auerbach

  2. Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Claire Attwooll & John Petrini

  3. Institute of Human Genetics, University of Wuerzburg, Germany

    Kornelia Neveling, Reinhard Kalb & Detlev Schindler

  4. Department of Pediatric Oncology, Hematology and Immunology, Children's Hospital, Heinrich Heine University, Duesseldorf, Germany

    Paula Rio, Eunike Velleuer & Helmut Hanenberg

  5. Laboratory of Statistical Genetics, The Rockefeller University, New York, New York, USA

    Sandra Barral & Jurg Ott

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  1. Orna Levran
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Correspondence to Arleen D Auerbach.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Chromatograms displaying the wild type and mutation c.2533C>T in exon 17 of BRIP1, and illustration of the creation of a premature stop codon R798X. (PDF 106 kb)

Supplementary Methods (PDF 77 kb)

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Levran, O., Attwooll, C., Henry, R. et al. The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia. Nat Genet 37, 931–933 (2005). https://doi.org/10.1038/ng1624

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