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Journal articles
Effects of Uracil Incorporation, DNA Mismatches, and Abasic Sites on Cleavage and Religation Activities of Mammalian Topoisomerase I
Abstract : Abasic sites and deamination of cytosine to uracil are probably the most common types of endogenous DNA damage. The effects of such lesions on DNA topoisomerase I (top1) activity were examined in oligonucleotides containing a unique top1 cleavage site. The presence of uracils and abasic sites within the first 4 bases immediately 5' to the cleavage site suppressed normal top1 cleavage and induced new top1 cleavage sites. Uracils immediately 3' to the cleavage site increased cleavage and produced a camptothecin mimicking effect. A mismatch with a bulge or abasic sites immediately 3' to the top1 cleavage site irreversibly trapped top1 cleavable complexes in the absence of camptothecin and produced a suicide cleavage complex. These results demonstrate that top1 activity is sensitive to physiological, environmental, and pharmacological DNA modifications and that top1 can act as a specific mismatch- and abasic site-nicking enzyme.
https://www.hal.inserm.fr/inserm-02438217
Contributor : Philippe Pourquier <>
Submitted on : Tuesday, January 14, 2020 - 10:28:27 AM
Last modification on : Thursday, January 16, 2020 - 1:31:17 AM
Contributor : Philippe Pourquier <>
Submitted on : Tuesday, January 14, 2020 - 10:28:27 AM
Last modification on : Thursday, January 16, 2020 - 1:31:17 AM
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