کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1981227 | 1061908 | 2009 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Apex1 can cleave complex clustered DNA lesions in cells
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کلمات کلیدی
Clustered lesionsDSBMultiply damaged sites8oxoGBERBPSFPGAPEX1SSBoligodeoxyribonucleotideAP Endonuclease8-oxo-7,8-dihydroguanine - 8-اکسو-7،8-دی هیدروگوانینAbasic - آبادیOligonucleotide - اولیگونوکلئوتیدTetrahydrofuran - تتراهیدروفورانDNA repair - ترمیم DNAbase excision repair - تعمیر پایه پایهbase pairs - جفت پایهdouble strand break - شکست دو رشتهsingle strand break - شکستن تک رشتهformamidopyrimidine DNA glycosylase - فرمامیدوپیریمیدین دی ان ای گلیکوزیلازFuran - فوران
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Current data indicate that clustered DNA damage generated by ionizing radiation contains 2-5 damages within 20Â bps. The complexity of clustered damage is also believed to increase as the linear energy transfer of the radiation increases. Complex lesions are therefore biologically relevant especially with the use of carbon ion beam therapy to treat cancer. Since two closely opposed AP site analogs (furans) are converted to a double strand break (DSB) in cells, we hypothesized that breakage could be compromised by increasing the complexity of the cluster. We have examined the repair of clusters containing three and four lesions in mouse fibroblasts using a luciferase reporter plasmid. The addition of a third furan did reduce but not eliminate cleavage, while a tandem 8-oxo-7,8-dihydroguanine (8oxoG) immediately 5â² to one furan in a two or three furan cluster decreased DSB formation by a small amount. In vitro studies using nuclear extracts demonstrated that the tandem 8oxoG was not removed under conditions where the furan was cleaved, but the presence of the 8oxoG reduced cleavage at the furan. Interestingly, a cluster of an 8oxoG opposite a furan did not form a DSB in cells. We have shown that Apex1 can cleave these complex clustered lesions in cells. This therefore indicates that Apex1 can generate complex DSBs from clustered lesions consisting of base damage and AP sites. Repair of these complex DSBs may be compromised by the nearby oxidative damage resulting in potentially lethal and biologically relevant damage.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 8, Issue 12, 3 December 2009, Pages 1343-1354
Journal: DNA Repair - Volume 8, Issue 12, 3 December 2009, Pages 1343-1354
نویسندگان
Svitlana Malyarchuk, Reneau Castore, Lynn Harrison,