The Fanconi anemia gene product FANCF is a flexible adaptor protein

France Léveillé, Eric Blom, Annette L. Medhurst, Patrick Bier, El Houari Laghmani, Mark Johnson, Martin A. Rooimans, Alexandra Sobeck, Quinten Waisfisz, Fré Arwert, K. J. Patel, Maureen E. Hoatlin, Hans Joenje, Johan P. De Winter

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

The Fanconi anemia (FA) protein FANCF is an essential component of a nuclear core complex that protects the genome against chromosomal instability, but the specific function of FANCF is still poorly understood. Based upon the homology between human and Xenopus laevis FANCF, we carried out an extensive mutagenesis study to examine which domains are functionally important and to gain more insight into the function of FANCF. In contrast to previous suggestions, we show that FANCF does not have a ROM-like function. We found that the C terminus of FANCF interacts directly with FANCG and allows the assembly of other FA proteins into a stable complex. The N terminus appears to stabilize the interaction with FANCA and FANCG and is essential for the binding of the FANCC/FANCE subcomplex. We identified several important amino acids in this N-terminal region but, surprisingly, many amino acid changes failed to affect the function of the FANCF protein. Our data demonstrate that FANCF acts as a flexible adaptor protein that plays a key role in the proper assembly of the FA core complex.

Original languageEnglish (US)
Pages (from-to)39421-39430
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number38
DOIs
StatePublished - Sep 17 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Léveillé, F., Blom, E., Medhurst, A. L., Bier, P., Laghmani, E. H., Johnson, M., Rooimans, M. A., Sobeck, A., Waisfisz, Q., Arwert, F., Patel, K. J., Hoatlin, M. E., Joenje, H., & De Winter, J. P. (2004). The Fanconi anemia gene product FANCF is a flexible adaptor protein. Journal of Biological Chemistry, 279(38), 39421-39430. https://doi.org/10.1074/jbc.M407034200