ENZYMATIC-REACTION WITH UNNATURAL SUBSTRATES - DNA PHOTOLYASE (ESCHERICHIA-COLI) RECOGNIZES AND REVERSES THYMINE[2+2]DIMERS IN THE DNA STRAND OF A DNA PNA HYBRID DUPLEX/

Peptide nucleic acids (PNA) are mimics with normal bases connected to a pseudopeptide chain that obey Watson-Crick rules to form stable dupl exes with itself and natural nucleic acids. This has focused attention on PNA as therapeutic or diagnostic reagents. Duplexes formed with PN A mirror some but not all properties of DNA, One fascinating aspect of PNA biochemistry is their reaction with enzymes. Here we show an enzy me reaction that operates effectively on a PNA/DNA hybrid duplex. A DN A oligonucleotide containing a cis, syn-thymine [2+2] dimer forms a st able duplex with PNA, The hybrid duplex is recognized by photolyase, a nd irradiation of the complex leads to the repair of the thymine dimer . This finding provides insight into the enzyme mechanism and provides a means for the selective repair of thymine photodimers.