Biological consequences of potential repair intermediates of clustered base damage site in Escherichia coli

Shikazono, Naoya; O'Neill, P.*

To gain insights into the processing of bistranded base lesions, several potential repair intermediates following 8-oxoG removal from bistranded clusters containing 8-oxoG and DHT were assessed. Clusters, such as DHT/AP and DHT/GAP have relatively low mutation frequencies, whereas clusters, such as AP/AP or GAP/AP, significantly reduce the number of transformed colonies, most probably through formation of a lethal DSB. These results suggest that bistranded base lesions, but not clusters containing only AP sites and strand breaks, are repaired in a coordinated manner so that the formation of DSBs is avoided. We propose that, when either base lesion is initially excised from a bistranded base damage site, the remaining base lesion will only rarely be converted into an AP site or a single strand break in vivo.