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• W1970867145 abstract "During mitosis, equal segregation of chromosomes depends on proper kinetochore-microtubule attachments. Merotelic kinetochore orientation, in which a single kinetochore binds microtubules from both spindle poles [1Gregan J. Polakova S. Zhang L. Tolić-Nørrelykke I.M. Cimini D. Merotelic kinetochore attachment: causes and effects.Trends Cell Biol. 2011; 21: 374-381Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar], is a major cause of chromosome instability [2Cimini D. Howell B. Maddox P. Khodjakov A. Degrassi F. Salmon E.D. Merotelic kinetochore orientation is a major mechanism of aneuploidy in mitotic mammalian tissue cells.J. Cell Biol. 2001; 153: 517-527Crossref PubMed Scopus (399) Google Scholar], which is commonly observed in solid tumors [3Thompson S.L. Bakhoum S.F. Compton D.A. Mechanisms of chromosomal instability.Curr. Biol. 2010; 20: R285-R295Abstract Full Text Full Text PDF PubMed Scopus (392) Google Scholar, 4Thompson S.L. Compton D.A. Examining the link between chromosomal instability and aneuploidy in human cells.J. Cell Biol. 2008; 180: 665-672Crossref PubMed Scopus (358) Google Scholar]. Using the fission yeast Schizosaccharomyces pombe, we show that a proper force balance between kinesin motors on interpolar spindle microtubules is critical for correcting merotelic attachments. Inhibition of the plus-end-directed spindle elongation motors kinesin-5 (Cut7) and kinesin-6 (Klp9) reduces spindle length, tension at kinetochores, and the frequency of merotelic attachments. In contrast, merotely is increased by deletion of the minus-end-directed kinesin-14 (Klp2) or overexpression of Klp9. Also, Cdk1 regulates spindle elongation forces to promote merotelic correction by phosphorylating and inhibiting Klp9. The role of spindle elongation motors in merotelic correction is conserved, because partial inhibition of the human kinesin-5 homolog Eg5 using the drug monastrol reduces spindle length and lagging chromosome frequency in both normal (RPE-1) and tumor (CaCo-2) cells. These findings reveal unexpected links between spindle forces and correction of merotelic attachments and show that pharmacological manipulation of spindle elongation forces might be used to reduce chromosome instability in cancer cells." @default.
• W1970867145 created "2016-06-24" @default.
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• W1970867145 date "2012-02-01" @default.
• W1970867145 modified "2023-10-12" @default.
• W1970867145 title "A Role for Metaphase Spindle Elongation Forces in Correction of Merotelic Kinetochore Attachments" @default.
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• W1970867145 doi "https://doi.org/10.1016/j.cub.2011.12.022" @default.
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