Inhibition of a DNA-helicase by peptide nucleic acids

Bis-peptide nucleic acid (bis-PNA) binding results in D-loop formation by s trand displacement at complementary homopurine stretches in DNA duplexes. T ranscription and replication in intact cells is mediated by multienzymatic complexes involving several proteins other than polymerases. The behaviour of the highly stable clamp structure formed by bis-PNAs has thus far been s tudied with respect to their capacity to arrest RNA polymerases. Little att ention has been given to their recognition and processing by DNA helicases. In this report we have investigated the inhibitory effect of a bis-PNA on the DNA-helicase activity of the well characterized herpes simplex type I U L9 protein. Unwinding by UL9 of a synthetic substrate is significantly inhi bited by a bis-PNA and the addition of the ICP8 protein, which increases UL 9 processivity, does not relieve this inhibition.