The SUMO protease SENP1 is required for cohesion maintenance and mitotic arrest following spindle poison treatment

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• 作者：Saho Era ; Takuya Abe ; Hiroshi Arakawa ; Shunsuke Kobayashi ; Barnabas Szakal ; Yusuke Yoshikawa ; Akira Motegi ; Shunichi Takeda ; Dana Branzei
• 关键词：SENPs ; Spindle poisons ; Mitotic slippage ; Cohesion maintenance ; Plk1 kinase ; DT40 cells
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 出版时间：28 September, 2012
• 年：2012
• 卷：426
• 期：3
• 页码：310-316
• 全文大小：792 K

文摘

SUMO conjugation is a reversible posttranslational modification that regulates protein function. SENP1 is one of the six SUMO-specific proteases present in vertebrate cells and its altered expression is observed in several carcinomas. To characterize SENP1 role in genome integrity, we generated Senp1 knockout chicken DT40 cells. SENP1^?/? cells show normal proliferation, but are sensitive to spindle poisons. This hypersensitivity correlates with increased sister chromatid separation, mitotic slippage, and apoptosis. To test whether the cohesion defect had a causal relationship with the observed mitotic events, we restored the cohesive status of sister chromatids by introducing the TOP2¦Á^+/? mutation, which leads to increased catenation, or by inhibiting Plk1 and Aurora B kinases that promote cohesin release from chromosomes during prolonged mitotic arrest. Although TOP2¦Á is SUMOylated during mitosis, the TOP2¦Á^+/? mutation had no obvious effect. By contrast, inhibition of Plk1 or Aurora B rescued the hypersensitivity of SENP1^?/? cells to colcemid. In conclusion, we identify SENP1 as a novel factor required for mitotic arrest and cohesion maintenance during prolonged mitotic arrest induced by spindle poisons.