Securin is required for chromosomal stability in human cells

被引:343
作者
Jallepalli, PV
Waizenegger, IC
Bunz, F
Langer, S
Speicher, MR
Peters, JM
Kinzler, KW
Vogelstein, B
Lengauer, C
机构
[1] Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA
[2] Howard Hughes Med Inst, Baltimore, MD 21231 USA
[3] Res Inst Mol Pathol, A-1030 Vienna, Austria
[4] Univ Munich, Inst Anthropol & Human Genet, D-80333 Munich, Germany
关键词
D O I
10.1016/S0092-8674(01)00340-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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收藏
页码:445 / 457
页数:13
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