In situ enzymatic reclosure of opened imidazole rings of purines in DNA damaged by gamma-irradiation

Abstract

When aqueous solutions of DNA were treated with 10-500 grays of gamma-rays, the imidazole rings of some adenine and guanine residues underwent scission, resulting in the conversion of these purines to formamidopyrimidines. It was found that formamidopyrimidine-DNA glycosylase, known to remove imidazole-ring-opened 7-methylguanine from DNA, did not excise the radiation-induced non-alkylated formamidopyrimidines formed for adenine and guanine. The repair of these ring-opened purines was found to involve an enzymatic recyclizing of the opened imidazole ring that effects a restoration of the C-8 to N-9 bond. The enzyme, purine imidazole-ring cyclase reclosed the imidazole rings of 90% of ring-opened adenine or guanine, but did not close the opened imidazole ring of 7-methylguanine-derived formamidopyrimidine in DNA.