Abstract:
:Ionizing radiation induces clustered DNA damage sites, whereby two or more individual DNA lesions are formed within one or two helical turns of DNA by a single radiation track. A subset of DNA clustered damage sites exist in which the lesions are located in tandem on the same DNA strand. Recent studies have established that two closely opposed lesions impair the repair machinery of the cell, but few studies have investigated the processing of tandem lesions. In this study, synthetic double-stranded oligonucleotides were synthesized to contain 8-oxoA and an AP site in tandem, separated by up to four bases in either a 5' or 3' orientation. The influence 8-oxoA has on the incision of the AP site by the E. coli glycosylases Fpg and Nth protein and the human AP endonuclease HAP1 was assessed. 8-OxoA has little or no effect on the efficiency of incision of the AP site by Nth protein; however, the efficiency of incision of the AP site by Fpg protein is reduced in the presence of 8-oxoA even up to a four-base separation in both the 5' and 3' orientations. 8-OxoA influences the efficiency of HAP1 incision of the AP site only when it is 3' to the AP site and separated by up to two bases. This study demonstrates that the initial stages of base excision repair can be impaired by the presence of a second base lesion in proximity to an AP site on the same DNA strand. This impairment could have biological consequences, such as mutation induction, if the AP site is present at replication.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Lomax ME,Salje H,Cunniffe S,O'Neill Pdoi
10.1667/rr3284subject
Has Abstractpub_date
2005-01-01 00:00:00pages
79-84issue
1eissn
0033-7587issn
1938-5404pii
RR3284journal_volume
163pub_type
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journal_title:Radiation research
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pub_type: 杂志文章
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更新日期:2000-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:1999-12-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1667/RR3291.1
更新日期:2013-07-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章,评审
doi:10.1667/RR1470.1
更新日期:2009-02-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1983-11-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
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pub_type: 杂志文章
doi:
更新日期:1995-05-01 00:00:00
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pub_type: 杂志文章
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
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更新日期:2020-04-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1984-12-01 00:00:00
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更新日期:2009-05-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2000-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:2001-03-01 00:00:00