A MUTANT STRAIN OF MOUSE FM3A CELLS DEFECTIVE IN APOPTOTIC DNA FRAGMENTATION

A mutant strain of mouse FM3A cells was defective in apoptotic DNA fra gmentation. Upon DNA damage by UV-radiation, the strain did not form D NA fragments, though it accumulated a large amount of p53 protein as d id wild-type cells. No DNA fragmentation was observed when the strain was subjected to other kinds of DNA damaging agents such as X ray-radi ation, or addition of etoposide to the culture medium. Other well-know n biological stimulations inducing apoptosis, serum depletion or addit ion of TNF-alpha to the culture medium, also failed to cause DNA fragm entation in the cells. Using this apoptosis-deficient strain, we chara cterized another apoptotic reaction, export of phosphatidylserine to t he cell surface. This molecule was exported onto the surface in both w ild-type and the mutant cells when cells were treated with TNF-alpha a nd cycloheximide. Thus, the export of phosphatidylserine is suggested to be independent of the pathway for apoptotic DNA fragmentation. (C) 1998 Academic Press.