CORRECTION OF THE DNA-REPAIR DEFECT IN FANCONI-ANEMIA COMPLEMENTATIONGROUP-A AND GROUP-D CELLS

We have previously isolated from Fanconi anemia, complementation group s A (FA-A) and D (FA-D) cells, a DNA endonuclease complex which is def ective in its ability to incise DNA containing interstrand crosslinks produced by psoralen plus WA light. The repair capabilities of the FA complexes, compared with those of the corresponding normal complex, ha ve now been examined using two types of complementation analysis. Firs t, introduction of the normal complex, by electroporation, into 8-meth oxypsoralen (8-MOP) plus UVA treated FA-A and FA-D cells resulted in c orrection of their repair defect, determined by measuring repair-relat ed unscheduled DNA synthesis (UDS), The FA-A and FA-D complexes could similarly complement the repair defect in each others' cells, but not in their own. Second, mixing the normal with the FA-A and FAD complexe s, or the FA-A with the FA-D complex, in a cell-free system resulted i n correction of the defect in ability of these FA complexes to incise damaged DNA. These results indicate that the normal complex contains t he proteins needed to correct the DNA repair defect in FA-A and FA-D c ells and that the FA-A and FA-D complexes contain the protein needed t o complement the repair defect in each other. (C) 1997 Academic Press