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  • The EMBO Journal (2002) 21, 3414 - 3423
  • doi:10.1093/emboj/cdf355

FANCE: the link between Fanconi anaemia complex assembly and activity

Paul Pace1,6, Mark Johnson1,6, Wu Meng Tan1, Georgina Mosedale1, Chelvin Sng1, Maureen Hoatlin2, Johan de Winter3, Hans Joenje3, Fanni Gergely4 and K. J. Patel1,5

  1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK
  2. Division of Molecular Medicine and Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR 97201, USA
  3. Department of Clinical Genetics and Human Genetics, Free University Medical Center, NL-1081 BT Amsterdam, The Netherlands
  4. Wellcome Trust/Cancer Research UK Institute, Tennis Court Road, Cambridge, UK
  5. Department of Investigative Medicine, Addenbrookes Hospital, University of Cambridge, Hills Road, Cambridge, UK
  6. P.Pace and M.Johnson contributed equally to this work

Correspondence to:

K. J. Patel, E-mail: kjp@mrc-lmb.cam.ac.uk

Received 21 March 2002; Accepted 9 May 2002; Revised 9 May 2002

The Fanconi anaemia (FA) nuclear complex (composed of the FA proteins A, C, G and F) is essential for protection against chromosome breakage. It activates the downstream protein FANCD2 by monoubiquitylation; this then forges an association with the BRCA1 protein at sites of DNA damage. Here we show that the recently identified FANCE protein is part of this nuclear complex, binding both FANCC and FANCD2. Indeed, FANCE is required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2. Disease-associated FANCC mutants do not bind to FANCE, cannot accumulate in the nucleus and are unable to prevent chromosome breakage.

  • Keywords:

    • chromosome breakage,
    • FANCE,
    • Fanconi anaemia,
    • nuclear complex assembly