Functional deficiency of the FEN1 gene has been suggested to cause genomic instability
and cancer predisposition. We have identified a group of FEN1 mutations in human cancer
specimens. Most of these mutations abrogated two of three nuclease activities of flap
endonuclease 1 (FEN1). To demonstrate the etiological significance of these somatic
mutations, we inbred a mouse line harboring the E160D mutation representing mutations
identified in human cancers. Selective elimination of nuclease activities led to frequent …