The role of SNM1 family nucleases in etoposide-induced apoptosis |
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| Authors: | Hosono Yoshifumi Abe Takuya Ishiai Masamichi Takata Minoru Enomoto Takemi Seki Masayuki |
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| Institution: | aMolecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan;bIFOM, The FIRC Institute for Molecular Oncology Foundation, IFOM-IEO Campus, Via Adamello 16, 20139 Milan, Italy;cLaboratory of DNA Damage Signaling, Department of Late Effect Studies, Radiation Biology Center, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan;dMolecular Cell Biology Laboratory, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan |
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| Abstract: | DNA double strand breaks (DSBs) induced by etoposide, an inhibitor of DNA topoisomerase II, are repaired mainly by non-homologous end joining (NHEJ). Unexpectedly, it was found that at high doses of etoposide, proteins involved in NHEJ, such as KU70/80, DNA-PKcs and ARTEMIS/SNM1C, trigger apoptosis rather than repair of DSBs. Because ARTEMIS is a member of the SNM1 protein family that includes SNM1A and APOLLO/SNM1B, this study examined whether SNM1A and/or APOLLO are also involved in etoposide-induced apoptosis. Using SNM1A−/− and APOLLO−/− cells, it was found that both SNM1A and APOLLO participate in etoposide-induced apoptosis. Although cell viability monitored by MTT assay did not differ between SNM1A−/−/APOLLO−/−/ARTEMIS−/−, SNM1A−/−/APOLLO−/−, and single gene knockout cells, DNA fragmentation monitored by TUNEL assay differed between these cells, suggesting that the three SNM1 family nucleases function independently, at least during the induction of apoptotic DNA fragmentation. |
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| Keywords: | Apoptosis SNM1A APOLLO ARTEMIS NHEJ DT40 |
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