Adapt or die: how eukaryotic cells respond to prolonged activation of the spindle assembly checkpoint. (24th November 2010)

• Record Type: Journal Article
• Authors: Rossio, Valentina; Galati, Elena; Piatti, Simonetta
• Is Part Of: Biochemical Society transactions. Volume 38:Number 6(2010)
• Page Start: 1645
• Page End: 1649
• Publication Date: 2010-11-24
• Subjects: adaptation -- antimitotic -- mitotic slippage -- spindle assembly checkpoint; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0381645
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : Many cancer-treating compounds used in chemotherapies, the so-called antimitotics, target the mitotic spindle. Spindle defects in turn trigger activation of the SAC (spindle assembly checkpoint), a surveillance mechanism that transiently arrests cells in mitosis to provide the time for error correction. When the SAC is satisfied, it is silenced. However, after a variable amount of time, cells escape from the mitotic arrest, even if the SAC is not satisfied, through a process called adaptation or mitotic slippage. Adaptation weakens the killing properties of antimitotics, ultimately giving rise to resistant cancer cells. We summarize here the mechanisms underlying this process and propose a strategy to identify the factors involved using budding yeast as a model system. Inhibition of factors involved in SAC adaptation could have important therapeutic applications by potentiating the ability of antimitotics to cause cell death.