New players of the mitotic checkpoint in s. Pombe

Abstract

The Mitotic Checkpoint or Spindle Assembly Checkpoint (SAC) is a surveillance mechanism that contributes to the preservation of genomic stability by delaying the timing of mitotic exit until all chromosomes are properly attached to the mitotic spindle apparatus. A defective SAC results in embryonic lethality and premature ageing in mouse models. In human cell culture, a defective SAC leads to a drastic increase in the appearance of aneuploidy. During cancer evolution, aneuploidies are thought to allow the clonal expansion of those tumour cells with chromosome combinations that provide increased proliferation potential, invasiveness as well as drug resistance among others. In this thesis, using the fission yeast as a model organism, we have explored a mechanism by which Mitogen-Activated Protein kinase (MAPK) pathways might regulate the activity of the SAC.