title: The role of SNM1 family nucleases in etoposide-induced apoptosis.
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.
authors.affiliation: Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Sendai, Miyagi 980-8578, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Hosono
authors.forename: Takuya
authors.initials: T
authors.lastname: Abe
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ishiai
authors.forename: Minoru
authors.initials: M
authors.lastname: Takata
authors.forename: Takemi
authors.initials: T
authors.lastname: Enomoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Seki
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002645:Chickens; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005047:Etoposide / Q000494:pharmacology*; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000502:physiology*; D055786:Gene Knockout Techniques; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; C426344:DCLRE1C protein, human; D004720:Endonucleases; D005090:Exodeoxyribonucleases; D045643:DNA Repair Enzymes