The Fanconi anemia gene product FANCF is a flexible adaptor protein.
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.
Léveillé
France
F
Department of Clinical Genetics and Human Genetics, VU University Medical Center, Van der Boechorststraat 7, NL-1081BT Amsterdam, The Netherlands.
Blom
Eric
E
Medhurst
Annette L
AL
Bier
Patrick
P
Laghmani
El Houari
el H
Johnson
Mark
M
Rooimans
Martin A
MA
Sobeck
Alexandra
A
Waisfisz
Quinten
Q
Arwert
Fré
F
Patel
K J
KJ
Hoatlin
Maureen E
ME
Joenje
Hans
H
de Winter
Johan P
JP
D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000502:physiology*; D052219:Fanconi Anemia Complementation Group F Protein; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014981:Xenopus
C499901:FANCF protein, human; D052219:Fanconi Anemia Complementation Group F Protein; D016601:RNA-Binding Proteins