Biological consequences of bistranded clustered DNA damage in

Shikazono, Naoya; Pearson, C.*; Thacker, J.*; O'Neill, P.*

Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Using a plasmid-based assay in , we found a significantly higher mutation frequency for the clustered DHT + 8-oxoG lesions than that for either a single 8-oxoG or a single DHT in wild-type and in glycosylase-deficient strains of . To gain further insights on the processing of the DHT + 8-oxoG cluster, several potential intermediates after 8-oxoG removal were assessed. DHT + AP or DHT + Gap containing cluster had a relatively low mutation frequency, whereas AP + AP or Gap + AP cluster was found to strongly retard replication. These results led us to suggest that, when either 8-oxoG or DHT is initially excised from a cluster containing 8-oxoG and DHT, the remaining base damage will not be further converted to an AP site or to a single strand break .