Differential Effects of Procaine and Phenethyl Alcohol on Excision Repair of DNA in u.v.-irradiatedEscherichia Coli

Abstract

Experiments were performed to investigate the involvement of the cell membrane in the excision DNA repair process in Escherichia coli. Two membrane-binding drugs, procaine and phenethyl alcohol (PEA), inhibited liquid-holding recovery (LHR) in u.v.-irradiated E. coli wild-type and recA strains. In uvrB and polA strains where, after u.v.-irradiation, LHR was absent the two drugs had no effect. Both drugs markedly reduced the removal of u.v.-induced thymine dimers in the DNA of wild-type cells (H/r30). Analysis by alkaline sucrose gradients revealed that PEA inhibited the incision step in excision repair. In contrast, procaine had no effect on incision but apparently inhibited the late steps in excision repair. PEA dissociated DNA from the cell membrane, whereas procaine did not. The results suggest that the two drugs PEA and procaine inhibit LHR and the excision repair process operating on u.v.-induced damage in E. coli by at least two different mechanisms each of which may involve the cell membrane.

Nucleotide excision repair in Escherichia coli.

“…The UvrB subunit is a hydrophobic protein, which is cleaved by a membranebound protease (32,33). Yonei and co-workers, in a series of papers, have shown that membrane-disrupting drugs such as lidocaine, procaine, and phenethyl alcohol inhibit nucleotide excision repair (237,238,240). Phenethyl alcohol, which clearly disrupts the DNA-membrane association, was shown to inhibit the incision step, whereas procaine, which does not inhibit the membrane-DNA associations, was shown to inhibit a later excision or resynthesis step (240).…”