Closely opposed apurinic/apyrimidinic sites are converted to double strand breaks in Escherichia coli even in the absence of exonuclease III, endonuclease IV, nucleotide excision repair and AP lyase cleavage.

Multiply damaged sites (MDSs) consist of two or more damages within 20 base pairs (bps) and are introduced into DNA by ionizing radiation. Using a plasmid assay, we previously demonstrated that repair in Escherichia coli generated a double strand break (DSB) from two closely opposed uracils when uracil DNA glycosylase initiated repair. To identify the enzymes that converted the resulting apurinic/apyrimidinic (AP) sites to DSBs, repair was examined in bacteria deficient in AP site cleavage.

Two clustered 8-oxo-7,8-dihydroguanine (8-oxodG) lesions increase the point mutation frequency of 8-oxodG, but do not result in double strand breaks or deletions in Escherichia coli.

Multiply damaged sites (MDSs) are generated in DNA by ionizing radiation. In vitro studies predict that base excision repair in cells will convert MDSs to lethal double strand breaks (DSBs) when two opposing base damages are situated >/=2 bp apart. If the lesions are situated immediately 5' or 3' to each other, repair is predicted to occur sequentially due to inhibition of the DNA glycosylase by a single strand break repair intermediate.