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Shikazono, Naoya; Pearson, C.*; O'Neill, P.*; Thacker, J.*
Nucleic Acids Research, 34(13), p.3722 - 3730, 2006/08
Times Cited Count：57 Percentile：71.26(Biochemistry & Molecular Biology)no abstracts in English
Shikazono, Naoya; Pearson, C.*; Thacker, J.*; O'Neill, P.*
no journal, ,
no abstracts in English
Shikazono, Naoya; Pearson, C.*; Thacker, J.*; O'Neill, P.*
no journal, ,
Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Recent 
studies have shown that the repair of lesions within clusters may be retarded, but less is known about the processing and the mutagenic effects of such clustered damage in vivo. Using a bacterial plasmid-based assay, we have investigated the mutagenic potential of bistranded clustered damage sites which consist of 8-oxo-7,8-dihydroguanine (8-oxoG) and dihydrothymine (DHT) at defined separations. 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 
. From these results and similarities with the mutability of respective 8-oxoG + AP clusters, it is suggested that removal of 8-oxoG within clustered damage site is retarded, probably reflecting the preferential excision of DHT initially. For a certain fraction of clusters, 8-oxoG may be initially removed from the cluster. To gain further insights on the processing of the DHT + 8-oxoG cluster, several potential intermediates after 8-oxoG removal were assessed for their mutability. For instance, DHT + AP or DHT + Gap containing cluster, but not AP + AP or Gap +AP clusters, has a relatively low mutation frequency. Further, AP + AP or Gap + AP cluster had a reduced transformation efficiency. 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 base remaining within the resulting damage will not be further converted to an AP site or to a single strand break 
.
Shikazono, Naoya; Pearson, C.*; Thacker, J.*; O'Neill, P.*
no journal, ,
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 .
Shikazono, Naoya; Pearson, C.*; Thacker, J.*; O'Neill, P.*
no journal, ,
Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Recent in vitro studies have shown that the repair of lesions within clusters may be retarded, but less is known about the processing and the mutagenic effects of such clustered damage in vivo. Using a plasmid-based assay in Escherichia coli, we have investigated the mutagenic potential of bistranded clustered damage sites which consist of 8-oxo-7,8-dihydroguanine (8-oxoG) and dihydrothymine (DHT) at defined separations. 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 . Similar results were obtained with the 8-oxoG + AP cluster. To gain further insights on the processing of the DHT + 8-oxoG cluster, several potential intermediates were assessed. It was found that AP + AP and Gap + AP clusters strongly retard replication. These results led us to suggest that the base remaining within the cluster after removal of one of the base damage will not be further converted to an AP site or to a single strand break .
Shikazono, Naoya; Pearson, P.*; Thacker, J.*; O'Neill, P.*
no journal, ,
To gain insights on the processing of the DHT + 8-oxoG cluster in vivo, several potential intermediates after removal of base lesions were assessed for their transformation efficiency and mutability in the wild type strain of . DHT + AP or DHT + Gap containing cluster demonstrated relatively low mutation frequency. On the other hand, in the case of an AP + AP or Gap + AP cluster, in which a base damage is absent, transformation efficiencies were significantly reduced. From these results it is suggested that, when either 8-oxoG or DHT is initially excised from a cluster containing 8-oxoG and DHT, the modified base remaining within the resulting damage will not be converted into an AP site or to a single strand break in vivo.
