Effects of Uracil Incorporation, DNA Mismatches, and Abasic Sites on Cleavage and Religation Activities of Mammalian Topoisomerase I
| Autor: | Li-Ming Ueng, Kurt W. Kohn, Glenda Kohlhagen, Abhijit Mazumder, Yves Pommier, Philippe Pourquier, Malini Gupta |
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| Přispěvatelé: | Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Division of Basic Sciences [Belhesda, MA, USA] (Laboratory of Molecular Pharmacology), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Pourquier, Philippe, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) |
| Rok vydání: | 1997 |
| Předmět: |
DNA damage
[SDV]Life Sciences [q-bio] Deamination Cleavage (embryo) Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Uracil Molecular Biology 030304 developmental biology Mammals 0303 health sciences Binding Sites biology Oligonucleotide Hydrolysis Topoisomerase Nucleic Acid Heteroduplexes DNA Cell Biology [SDV] Life Sciences [q-bio] DNA Topoisomerases Type I chemistry 030220 oncology & carcinogenesis biology.protein Cytosine |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 1997, 272 (12), pp.7792-7796. ⟨10.1074/jbc.272.12.7792⟩ |
| ISSN: | 0021-9258 1083-351X |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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