An AP site can protect against the mutagenic potential of 8-oxoG when present within a tandem clustered site in E. coli.
Ionizing radiation induces clustered DNA damaged sites, defined as two or more lesions formed within one or two helical turns of the DNA through passage of a single radiation track. It is now established that clustered DNA damage sites are found in cells and present a challenge to the repair machine...
| Main Authors: | , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2007
|
| _version_ | 1797091676729114624 |
|---|---|
| author | Cunniffe, S Lomax, M O'Neill, P |
| author_facet | Cunniffe, S Lomax, M O'Neill, P |
| author_sort | Cunniffe, S |
| collection | OXFORD |
| description | Ionizing radiation induces clustered DNA damaged sites, defined as two or more lesions formed within one or two helical turns of the DNA through passage of a single radiation track. It is now established that clustered DNA damage sites are found in cells and present a challenge to the repair machinery of the cell but to date, most studies have investigated the effects of bi-stranded lesions. A subset of clustered DNA damaged sites exist in which two or more lesions are present in tandem on the same DNA strand. In this study synthetic oligonucleotides containing an AP site 1, 3 or 5 bases 5' or 3' to 8-oxo-7,8-dihydroguanine (8-oxoG) on the same DNA strand were synthesized as a model of a tandem clustered damaged sites. It was found that 8-oxoG retards the incision of the AP site by exonuclease III (Xth) and formamidopyrimidine DNA glycosylase (Fpg). In addition the rejoining of the AP site by xrs5 nuclear extracts is impaired by the presence of 8-oxoG. The mutation frequency arising from 8-oxoG within a tandem clustered site was determined in both wild type and mutant E. coli backgrounds. In wild-type, nth, fpg and mutY null E. coli, the mutation frequency is slightly elevated when an AP site is in tandem to 8-oxoG, compared with when 8-oxoG is present as a single lesion. Interestingly, in the double mutant mutY/fpg null E. coli, the mutation frequency of 8-oxoG is reduced when an AP site is present in tandem compared with when 8-oxoG is present as a single lesion. This study demonstrates that tandem lesions can present a challenge to the repair machinery of the cell. |
| first_indexed | 2024-03-07T03:36:25Z |
| format | Journal article |
| id | oxford-uuid:bc729068-e75a-4ff2-b42c-6954c7f42747 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:36:25Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:bc729068-e75a-4ff2-b42c-6954c7f427472022-03-27T05:24:23ZAn AP site can protect against the mutagenic potential of 8-oxoG when present within a tandem clustered site in E. coli.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bc729068-e75a-4ff2-b42c-6954c7f42747EnglishSymplectic Elements at Oxford2007Cunniffe, SLomax, MO'Neill, PIonizing radiation induces clustered DNA damaged sites, defined as two or more lesions formed within one or two helical turns of the DNA through passage of a single radiation track. It is now established that clustered DNA damage sites are found in cells and present a challenge to the repair machinery of the cell but to date, most studies have investigated the effects of bi-stranded lesions. A subset of clustered DNA damaged sites exist in which two or more lesions are present in tandem on the same DNA strand. In this study synthetic oligonucleotides containing an AP site 1, 3 or 5 bases 5' or 3' to 8-oxo-7,8-dihydroguanine (8-oxoG) on the same DNA strand were synthesized as a model of a tandem clustered damaged sites. It was found that 8-oxoG retards the incision of the AP site by exonuclease III (Xth) and formamidopyrimidine DNA glycosylase (Fpg). In addition the rejoining of the AP site by xrs5 nuclear extracts is impaired by the presence of 8-oxoG. The mutation frequency arising from 8-oxoG within a tandem clustered site was determined in both wild type and mutant E. coli backgrounds. In wild-type, nth, fpg and mutY null E. coli, the mutation frequency is slightly elevated when an AP site is in tandem to 8-oxoG, compared with when 8-oxoG is present as a single lesion. Interestingly, in the double mutant mutY/fpg null E. coli, the mutation frequency of 8-oxoG is reduced when an AP site is present in tandem compared with when 8-oxoG is present as a single lesion. This study demonstrates that tandem lesions can present a challenge to the repair machinery of the cell. |
| spellingShingle | Cunniffe, S Lomax, M O'Neill, P An AP site can protect against the mutagenic potential of 8-oxoG when present within a tandem clustered site in E. coli. |
| title | An AP site can protect against the mutagenic potential of 8-oxoG when present within a tandem clustered site in E. coli. |
| title_full | An AP site can protect against the mutagenic potential of 8-oxoG when present within a tandem clustered site in E. coli. |
| title_fullStr | An AP site can protect against the mutagenic potential of 8-oxoG when present within a tandem clustered site in E. coli. |
| title_full_unstemmed | An AP site can protect against the mutagenic potential of 8-oxoG when present within a tandem clustered site in E. coli. |
| title_short | An AP site can protect against the mutagenic potential of 8-oxoG when present within a tandem clustered site in E. coli. |
| title_sort | ap site can protect against the mutagenic potential of 8 oxog when present within a tandem clustered site in e coli |
| work_keys_str_mv | AT cunniffes anapsitecanprotectagainstthemutagenicpotentialof8oxogwhenpresentwithinatandemclusteredsiteinecoli AT lomaxm anapsitecanprotectagainstthemutagenicpotentialof8oxogwhenpresentwithinatandemclusteredsiteinecoli AT oneillp anapsitecanprotectagainstthemutagenicpotentialof8oxogwhenpresentwithinatandemclusteredsiteinecoli AT cunniffes apsitecanprotectagainstthemutagenicpotentialof8oxogwhenpresentwithinatandemclusteredsiteinecoli AT lomaxm apsitecanprotectagainstthemutagenicpotentialof8oxogwhenpresentwithinatandemclusteredsiteinecoli AT oneillp apsitecanprotectagainstthemutagenicpotentialof8oxogwhenpresentwithinatandemclusteredsiteinecoli |