Inhibition of DNA decatenation, but not DNA damage, arrests cells at metaphase.
Inhibition of DNA decatenation, but not DNA damage, arrests cells at metaphase.
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DOI：
10.1016/j.molcel.2004.08.018
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发表时间：
2004-09
期刊：
影响因子：
16
通讯作者：
D. Skoufias;F. Lacroix;P. Andreassen;L. Wilson;R. Margolis
中科院分区：
文献类型：
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作者：
D. Skoufias;F. Lacroix;P. Andreassen;L. Wilson;R. Margolis
双链断裂造成的 DNA 损伤会导致哺乳动物细胞在分裂间期停滞。目前尚不清楚 DNA 损伤是否会阻止细胞有丝分裂。我们在此表明，HeLa、U2OS 和 HCT116 三种人类细胞系不会因 γ 辐射或阿霉素在有丝分裂期间诱导的双链断裂而延迟有丝分裂。然而，ICRF-193（一种不会损伤 DNA 的拓扑异构酶 II 抑制剂）可在中期发生持久停滞。 ICRF-193 的阻滞不伴随 Mad2 或 Bub1 向着丝粒的募集，也不伴随组蛋白 H2AX 的磷酸化，表明 ICRF-193 的阻滞不是由于纺锤体组装检查点的激活，也不是对 DNA 损伤的反应。 VP-16 是另一种去连接抑制剂，仅在浓度远高于诱导 DNA 损伤的浓度时才会诱导中期停滞。我们得出的结论是，在哺乳动物细胞中，串联失败而不是 DNA 损伤导致了中期停滞。
DNA damage by double-strand breaks induces arrest during interphase in mammalian cells. It is not clear whether DNA damage can arrest cells in mitosis. We show here that three human cell lines, HeLa, U2OS, and HCT116, do not delay in mitosis in response to double-strand breaks induced during mitosis by γ irradiation or by adriamycin. Durable arrest at metaphase occurs, however, with ICRF-193, a topoisomerase II inhibitor that does not damage DNA. Arrest with ICRF-193 is not accompanied by recruitment of Mad2 or Bub1 to kinetochores, nor by phosphorylation of the histone H2AX, indicating arrest by ICRF-193 is not due to activation of the spindle assembly checkpoint, nor is it a response to DNA damage. VP-16, another decatenation inhibitor, induces metaphase arrest only at concentrations well above those that induce DNA damage. We conclude that decatenation failure, but not DNA damage, creates metaphase arrest in mammalian cells.