DNA sequence selectivity of human topoisomerase I-mediated DNA cleavage induced by camptothecin
| Autor: | Megan Carver, Chandanamali Punchihewa, Danzhou Yang |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Cleavage factor
Oligonucleotides Cleavage and polyadenylation specificity factor Topoisomerase-I Inhibitor Response Elements Cleavage (embryo) Biochemistry chemistry.chemical_compound medicine Humans DNA Cleavage Enzyme Inhibitors Molecular Biology Base Sequence biology Oligonucleotide Topoisomerase Recombinant Proteins DNA Topoisomerases Type I chemistry For the Record biology.protein Camptothecin Hypoxia-Inducible Factor 1 Topoisomerase I Inhibitors DNA medicine.drug |
| Zdroj: | Protein Science. 18:1326-1331 |
| ISSN: | 1469-896X 0961-8368 |
| DOI: | 10.1002/pro.138 |
| Popis: | In probing the mechanism of inhibition of hypoxia inducible factor (HIF-1) by campothecins, we investigated the ability of human topoisomerase I to bind and cleave HIF-1 response element (HRE), which contains the known camptothecin-mediated topoisomerase I cleavage site 5′-TG. We observed that the selection of 5′-TG by human topoisomerase I and topotecan depends to a large extent on the specific flanking sequences, and that the presence of a G at the −2 position (where cleavage occurs between −1 and +1) prevents the HRE site from being a preferred site for such cleavage. Furthermore, the presence of −2 T/A can induce the cleavage at a less preferred TC or TA site. However, in the absence of a more preferred site, the HRE site is shown to be cleaved by human topoisomerase I in the presence of topotecan. Thus, it is implied that the −2 base has a significant influence on the selection of the camptothecin-mediated Topo I cleavage site, which can overcome the preference for +1G. While the cleavage site recognition has been known to be based on the concerted effect of several bases spanning the cleavage site, such a determining effect of an individual base has not been previously recognized. A possible base-specific interaction between DNA and topoisomerase I may be responsible for this sequence selectivity. |
| Databáze: | OpenAIRE |
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