title: Securin is required for chromosomal stability in human cells.
abstract: Abnormalities of chromosome number are the most common genetic aberrations in cancer. The mechanisms regulating the fidelity of mitotic chromosome transmission in mammalian cells are therefore of great interest. Here we show that human cells without an hSecurin gene lose chromosomes at a high frequency. This loss was linked to abnormal anaphases during which cells underwent repetitive unsuccessful attempts to segregate their chromosomes. The abnormal mitoses were associated with biochemical defects in the activation of separin, the sister-separating protease, rendering it unable to cleave the cohesin subunit Scc1 efficiently. These results illuminate the function of mammalian securin and show that it is essential for the maintenance of euploidy.
authors.affiliation: The Johns Hopkins Oncology Center, 1650 Orleans Street, Baltimore, MD 21231, USA.
authors.forename: P V
authors.initials: PV
authors.lastname: Jallepalli
authors.forename: I C
authors.initials: IC
authors.lastname: Waizenegger
authors.forename: F
authors.initials: F
authors.lastname: Bunz
authors.forename: S
authors.initials: S
authors.lastname: Langer
authors.forename: M R
authors.initials: MR
authors.lastname: Speicher
authors.forename: J M
authors.initials: JM
authors.lastname: Peters
authors.forename: K W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: B
authors.initials: B
authors.lastname: Vogelstein
authors.forename: C
authors.initials: C
authors.lastname: Lengauer
mesh_terms: D000595:Amino Acid Sequence; D000705:Anaphase / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002503:Centromere / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism*; D002869:Chromosome Aberrations / Q000235:genetics / Q000378:metabolism*; D025063:Chromosome Disorders; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D009687:Nuclear Proteins; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D012854:Sister Chromatid Exchange / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C490529:MCD1 protein, S cerevisiae; D009687:Nuclear Proteins; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins