RecQ5 Interacts with Rad51 and Is Involved in Resistance of Drosophila to Cisplatin Treatment
| Autor: | Katsumi Kawasaki, Eishi Funakoshi, Takehiko Shibata, Sayako Maruyama, Minoru Nakayama, Kenji Takeuchi, Noriko Ohkita, Eiko Akaboshi, Fumiaki Ito |
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| Rok vydání: | 2012 |
| Předmět: |
Pharmacology
Cisplatin Genetics biology DNA repair DNA damage fungi genetic processes Mutant RAD51 Pharmaceutical Science Helicase General Medicine In vitro Cell biology enzymes and coenzymes (carbohydrates) chemistry.chemical_compound chemistry health occupations biology.protein medicine biological phenomena cell phenomena and immunity DNA medicine.drug |
| Zdroj: | Biological and Pharmaceutical Bulletin. 35:2017-2022 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b12-00551 |
| Popis: | RecQ5 is a member of the RecQ family of DNA helicases. There are 5 RecQ members in humans. Defects in 3 of them, i.e., BLM, WRN, and RTS, cause Bloom, Werner, and Rothmund-Thomson syndromes, respectively. RECQL1 and RECQL5 have not been associated with any human disease, and their precise roles are unknown. Our previous study suggests that the lack of RecQ5, which is the Drosophila homolog of RECQL5, leads to the accumulation of DNA double-stranded breaks (DSBs). It is possible that RecQ5 is involved in DSB repair. However, little is known about this possible function of RecQ5 in DSB repair. Here, we report that Rad51 protein, which plays a critical role in DSB repair, interacted with RecQ5 in vitro and in vivo in Drosophila. The Rad51 protein interacted with the C-terminal region of RecQ5, as shown by the yeast two-hybrid method. Moreover, the C-terminal region of the RecQ5 protein and the central region of Rad51 interacted directly and specifically when examined by the glutathione-S-transferase pull-down method. Consistent with these results, when RecQ5 and Rad51 were co-expressed in Drosophila cells in culture, they became co-localized in nuclei and could be co-immunoprecipitated. Furthermore, RecQ5-deficient flies (recq5) were more sensitive to the chemotherapeutic agent cisplatin compared with wild-type ones. Also, Rad51 mutants (rad51) were more sensitive to cisplatin, with sensitivity similar to that of recq5 rad51 double mutants. These data suggest that RecQ5 and Rad51 in Drosophila functioned for survival after the flies had been treated with cisplatin. |
| Databáze: | OpenAIRE |
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