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A rapid and sensitive method to measure endonuclease activity comprising reacting a substrate suspected of having endonuclease activity with a synthetic nucleotide to induce endonuclease cleavage of the synthetic nucleotide followed by measurement of activity by carrying out a polymerase chain reaction (PCR). When no polymerase chain reaction takes place when carrying out the method it is indicative of no endonuclease activity in the substrate. Synthetic oligonucleotides, primers, and probes useful for carrying out the method are disclosed.