title: The SUMO protease SENP1 is required for cohesion maintenance and mitotic arrest following spindle poison treatment.
abstract: 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 TOP2α(+/-) 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 TOP2α is SUMOylated during mitosis, the TOP2α(+/-) 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.
authors.affiliation: Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan, Italy.
authors.forename: Saho
authors.initials: S
authors.lastname: Era
authors.forename: Takuya
authors.initials: T
authors.lastname: Abe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arakawa
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Barnabas
authors.initials: B
authors.lastname: Szakal
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Motegi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Dana
authors.initials: D
authors.lastname: Branzei
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency; D053903:DNA Breaks, Double-Stranded; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003703:Demecolcine / Q000494:pharmacology; D010450:Endopeptidases / Q000235:genetics / Q000502:physiology*; D042822:Genomic Instability; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D015739:Nocodazole / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D025842:SUMO-1 Protein / Q000235:genetics / Q000502:physiology*; D008941:Spindle Apparatus / Q000187:drug effects / Q000502:physiology*; D050257:Tubulin Modulators / Q000494:pharmacology; D014747:Vinblastine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077235:Vinorelbine; D000097722:Cohesins; D000097869:Polo-Like Kinase 1
chemical_list: D000951:Antigens, Neoplasm; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D003703:Demecolcine; D010450:Endopeptidases; D015739:Nocodazole; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D025842:SUMO-1 Protein; D050257:Tubulin Modulators; D014747:Vinblastine; D000077235:Vinorelbine; D000097722:Cohesins; D000097869:Polo-Like Kinase 1