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• W2145859809 abstract "Aneuploidy is defined as numerical abnormalities of chromosomes and is frequently (>90%) present in solid tumors. In general, tumor cells become increasingly aneuploid with tumor progression. It has been proposed that enhanced genomic instability at least contributes significantly to, if not requires, tumor progression. Two major modes for genomic instability are microsatellite instability (MIN) and chromosome instability (CIN). MIN is associated with DNA-level defects (e.g. mismatch repair defects), and CIN is associated with mitotic errors such as chromosome mis-segregation. The mitotic spindle assembly checkpoint (SAC) ensures that cells with defective mitotic spindles or defective interaction between the spindles and kinetochores do not initiate chromosomal segregation during mitosis. Thus, the SAC functions to protect the cell from chromosome mis-segregation and anueploidy during cell division. A loss of the SAC function results in gross aneuploidy, a condition from which cells with an advantage for proliferation will be selected. During the past several years, a flurry of genetic studies in mice and humans strongly support the notion that an impaired SAC causes enhanced genomic instabilities and tumor development. This review article summarizes the roles of key spindle checkpoint proteins {i.e. Mad1/Mad1L1, Mad2/Mad2L1, BubR1/Bub1B, Bub3/Bub3 [conventional protein name (yeast or human)/mouse protein name]} and the modulators (i.e. Chfr/Chfr, Rae1/Rae1, Nup98/Nup98, Cenp-E/CenpE, Apc/Apc) in genomic stability and suppression of tumor development, with a focus on information from genetically engineered mouse model systems. Further elucidation of molecular mechanisms of the SAC signaling has the potential for identifying new targets for rational anticancer drug design." @default.
• W2145859809 created "2016-06-24" @default.
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• W2145859809 creator A5049261569 @default.
• W2145859809 creator A5057836337 @default.
• W2145859809 date "2009-04-16" @default.
• W2145859809 modified "2023-10-13" @default.
• W2145859809 title "Enhanced genomic instabilities caused by deregulated microtubule dynamics and chromosome segregation: a perspective from genetic studies in mice" @default.
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• W2145859809 doi "https://doi.org/10.1093/carcin/bgp081" @default.
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