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Title :Dynamic behavior of DNA topoisomerase IIβ in response to DNA double-strand breaks
Authors :Morotomi-Yano, Keiko
Saito, Shinta
Adachi, Noritaka
Yano, Ken-ichi
Issue Date :9-Jul-2018
Citation jtitle :Scientific Reports
vol. :8
start page :10344
Abstract :DNA topoisomerase II (Topo II) is crucial for resolving topological problems of DNA and plays important roles in various cellular processes, such as replication, transcription, and chromosome segregation. Although DNA topology problems may also occur during DNA repair, the possible involvement of Topo II in this process remains to be fully investigated. Here, we show the dynamic behavior of human Topo IIβ in response to DNA double-strand breaks (DSBs), which is the most harmful form of DNA damage. Live cell imaging coupled with site-directed DSB induction by laser microirradiation demonstrated rapid recruitment of EGFP-tagged Topo IIβ to the DSB site. Detergent extraction followed by immunofluorescence showed the tight association of endogenous Topo IIβ with DSB sites. Photobleaching analysis revealed that Topo IIβ is highly mobile in the nucleus. The Topo II catalytic inhibitors ICRF-187 and ICRF-193 reduced the Topo IIβ mobility and thereby prevented Topo IIβ recruitment to DSBs. Furthermore, Topo IIβ knockout cells exhibited increased sensitivity to bleomycin and decreased DSB repair mediated by homologous recombination (HR), implicating the role of Topo IIβ in HR-mediated DSB repair. Taken together, these results highlight a novel aspect of Topo IIβ functions in the cellular response to DSBs.
URL :https://www.nature.com/articles/s41598-018-28690-6
Type Local :雑誌掲載論文
ISSN :20452322
Publisher :Nature Publishing Group
Rights :© The Author(s) 2018
URI :http://hdl.handle.net/2298/40061
Appears in Collections:Journal Article (Technology)
Please use this identifier to cite or link to this item: http://hdl.handle.net/2298/40061