A Leu554-to-Pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein.

Three cDNA transcripts corresponding to complementation group C of Fanconi anemia (FA) were recently cloned. We confirm that the correct reading frame was reported and that a protein of an apparent molecular mass of 60 kDa is translated. A T-to-C transition at base 1,661 in the open reading frame is the only change found to date in the FA(C) cell line, resulting in a codon substitution from leucine554 to proline. Using site directed in vitro mutagenesis, we demonstrate that this mutation completely abolishes the activity of the FACC protein as analyzed by functional complementation assay. The physiological significance of this mutation is thus confirmed.