Abstract: Briefly stated, the present invention provides novel compositions and methods for detecting target nucleic acid sequences utilizing adjacent sequence-enzyme molecules. Within one aspect of the present invention, oligonucleotide-enzyme fusion molecules are provided, comprising an enzyme capable of cleaving scissile linkages and an oligonucleotide having the structure (NA.sub.1).sub.x --S.sub.z --(NA.sub.2).sub.y wherein NA.sub.1 and NA.sub.2 are nucleic acid sequences, S is a scissile nucleic acid linkage, x, y and z are integers from 1 to 100 and n is an integer from 1 to 10.

Abstract: A method for determining whether a selected nucleic acid molecule differs by one or more nucleotides from a desired sequence (the desired sequence may be defined to be either a native (e.g., wild type) or non-native (e.g., mutant) nucleotide sequence). The potential difference between the selected nucleic acid molecule and the desired nucleic acid sequence may be due to a germ or somatic mutation and may be, for example, a substitution, deletion addition or transversion of one or more nucleotides. Thus, for example, the method is useful for detection of mutations in oncogenes or mutations in other genes of interest, such as the transmembrane conductance regulator gene, which is implicated in cystic fibrosis.