Securin is required for chromosomal stability in human cells

Prasad V. Jallepalli; Irene C. Waizenegger; Fred Bunz; Sabine Langer; Michael R. Speicher; Jan Michael Peters; Kenneth W. Kinzler; Bert Vogelstein; Christoph Lengauer

doi:10.1016/S0092-8674(01)00340-3

Securin is required for chromosomal stability in human cells

Prasad V. Jallepalli, Irene C. Waizenegger, Fred Bunz, Sabine Langer, Michael R. Speicher, Jan Michael Peters, Kenneth W. Kinzler, Bert Vogelstein, Christoph Lengauer

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	445-457
Number of pages	13
Journal	Cell
Volume	105
Issue number	4
DOIs	https://doi.org/10.1016/S0092-8674(01)00340-3
State	Published - May 18 2001

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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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.",

author = "Jallepalli, {Prasad V.} and Waizenegger, {Irene C.} and Fred Bunz and Sabine Langer and Speicher, {Michael R.} and Peters, {Jan Michael} and Kinzler, {Kenneth W.} and Bert Vogelstein and Christoph Lengauer",

note = "Funding Information: We would like to thank Leslie Meszler from the Cell Imaging Core Facility for excellent technical assistance. This work was supported by the Clayton Fund, the Concern Foundation, and NIH grants CA 43460, CA 57345, CA 62924, GM 41690, and GM07309. Research in the lab of J.-M.P. is supported by Boehringer Ingelheim and by grants from the Austrian Science Fund and the Austrian Research Promotion Fund. Research in the lab of M.R.S. is supported by the Deutsche Krebshilfe. Under an agreement between CalBiochem and Johns Hopkins University, K.W.K. and B.V. are entitled to a share of the sales royalty for the anti-p21 antibodies received by the University from CalBiochem. The terms of this arrangement are being managed by the University in accordance with its conflict of interest policies. P.V.J. is a fellow of the Damon Runyon-Walter Winchell Foundation's Cancer Research Fund. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2001",

month = may,

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doi = "10.1016/S0092-8674(01)00340-3",

language = "English (US)",

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AU - Jallepalli, Prasad V.

AU - Waizenegger, Irene C.

AU - Bunz, Fred

AU - Langer, Sabine

AU - Speicher, Michael R.

AU - Peters, Jan Michael

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Lengauer, Christoph

N1 - Funding Information: We would like to thank Leslie Meszler from the Cell Imaging Core Facility for excellent technical assistance. This work was supported by the Clayton Fund, the Concern Foundation, and NIH grants CA 43460, CA 57345, CA 62924, GM 41690, and GM07309. Research in the lab of J.-M.P. is supported by Boehringer Ingelheim and by grants from the Austrian Science Fund and the Austrian Research Promotion Fund. Research in the lab of M.R.S. is supported by the Deutsche Krebshilfe. Under an agreement between CalBiochem and Johns Hopkins University, K.W.K. and B.V. are entitled to a share of the sales royalty for the anti-p21 antibodies received by the University from CalBiochem. The terms of this arrangement are being managed by the University in accordance with its conflict of interest policies. P.V.J. is a fellow of the Damon Runyon-Walter Winchell Foundation's Cancer Research Fund. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2001/5/18

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N2 - 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.

AB - 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.

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