TNF-α overproduction in FA-C cells is not a secondary effect of hypersensitivity to cross-linking agents. (A) FANCC alanine substitutions are located in 3 highly conserved domains.2 M55 is a naturally occurring truncation mutant. All of the alanine mutants are known to fully complement FA-C cells in the MMC sensitivity test.2 (B) HSC536 cells were transduced with wild-type FANCC cDNA (bar 2), 2 naturally occurring FANCC mutant constructs (bar 1, L554P and bar 9, M55) and 6 engineered point mutant constructs. With the exception of the partially effective S249A mutant and the completely effective normal cDNA (“wild-type”), which normalized TNF production in FA-C cells, TNF-α levels remain high in all of the isogenic cells expressing the other alanine mutants and M55.
