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Journal Articles

The Roles of specific glycosylases in determining the mutagenic consequences of clustered DNA base damage

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

Oral presentation

Mutagenic potential of clustered DNA damage site in ${it Escherichia coli}$

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

no journal, , 

no abstracts in English

Oral presentation

Nuclear moments of the radioactive isotope $$^{131}$$La determined by collinear fast-beam laser spectroscopy

Iimura, Hideki; Schuessler, H. A.*; Buchinger, F.*; Cocolios, T.*; Crawford, J. E.*; Gulick, S.*; Lee, J. K. P.*; Levy, C. D. P.*; Pearson, M.*; Lioubimov, V.*; et al.

no journal, , 

We report measurements of the hyperfine structure constants of $$^{131}$$La (N=74) as an initial step to further exploring the neutron deficient rare-earth region where a sudden onset of nuclear deformation is predicted theoretically around N=74. This work is an extension of our earlier off-line experiments on $$^{135,137-139}$$La to on-line laser spectroscopy. The radioactive isotope $$^{131}$$La (T$$_{1/2}$$=59 min) was produced by means of a spallation reaction using a proton beam from TRIUMF cyclotron. The hyperfine spectra were observed by using the method of collinear fast-beam laser spectroscopy. From the obtained hyperfine constants, the nuclear moments of $$^{131}$$La were derived. In order to arrive at an understanding of the nuclear structure of $$^{131}$$La, we have carried out particle triaxial-rotor calculations. The results from the calculation reproduce well the experimental values when a triaxial shape is assumed for $$^{131}$$La.

Oral presentation

Mutagenic potential of clustered DNA damage site in ${it Escherichia coli}$

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 ${it in vitro}$ 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 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 ${it E. coli}$. 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 ${it in vivo}$.

Oral presentation

Biological consequences of bistranded clustered DNA damage in ${it Escherichia coli}$

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 ${it Escherichia coli}$, 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 ${it E. coli}$. 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 ${it in vivo}$.

Oral presentation

Processing of clustered DNA damage sites which consist of 8-oxoG and DHT in ${it Escherichia coli}$

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 ${it E. coli}$. 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 ${it in vivo}$.

6 (Records 1-6 displayed on this page)
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