Halenaquinone, a chemical compound that specifically inhibits the secondary DNA binding of RAD51
| Autor: | Satoshi Tashiro, Yoichi Nakao, Rob W. M. Van Soest, Takako Ishida-Takaku, Hidekazu Suzuki, Motoki Takaku, Hitoshi Kurumizaka, Shintaro Ishigami, Takashi Kainuma |
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| Rok vydání: | 2011 |
| Předmět: |
chemistry.chemical_classification
genetic processes RAD51 Cell Biology Biology medicine.disease_cause Molecular biology enzymes and coenzymes (carbohydrates) chemistry.chemical_compound Enzyme chemistry Biochemistry In vivo health occupations Genetics Nucleic acid medicine biological phenomena cell phenomena and immunity Carcinogenesis Gene DNA Function (biology) |
| Zdroj: | Genes to Cells. 16:427-436 |
| ISSN: | 1356-9597 |
| Popis: | Mutations and single-nucleotide polymorphisms affecting RAD51 gene function have been identified in several tumors, suggesting that the inappropriate expression of RAD51 activity may cause tumorigenesis. RAD51 is an essential enzyme for the homologous recombinational repair (HRR) of DNA double-strand breaks. In the HRR pathway, RAD51 catalyzes the homologous pairing between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), which is the central step of the HRR pathway. To identify a chemical compound that regulates the homologous-pairing activity of RAD51, in the present study, we screened crude extract fractions from marine sponges by the RAD51-mediated homologous-pairing assay. Halenaquinone was identified as an inhibitor of the RAD51 homologous-pairing activity. A surface plasmon resonance analysis indicated that halenaquinone directly bound to RAD51. Intriguingly, halenaquinone specifically inhibited dsDNA binding by RAD51 alone or the RAD51-ssDNA complex, but only weakly affected the RAD51-ssDNA binding. In vivo, halenaquinone significantly inhibited the retention of RAD51 at double-strand break sites. Therefore, halenaquinone is a novel type of RAD51 inhibitor that specifically inhibits the RAD51-dsDNA binding. |
| Databáze: | OpenAIRE |
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