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Biochemical and genetic analysis of spindle assembly checkpoint in Saccharomyces cerevisiae : dottorato di ricerca in medicina molecolare : tesi di dottorato

Nezi, Luigi <1979- >

Tesi o dissertazioni - 2008

ABSTRACT During normal proliferation, cells inherit a complete copy of the genome. The spindle assembly checkpoint (SAC) delays anaphase onset until all sister chromatid pairs have attained bipolar attachment to spindle microtubules. In this way the SAC coordinates mitotic progression with the process of sister chromatid alignment at metaphase. Defects in the SAC contribute to hallmarks of cancers such as chromosome instability and aneuplody. Anaphase is triggered by the proteolysis of one of the subunits of Cohesin by Separase, which is normally kept inactive by Securin. Securin ubiquitination by APC/C leads to anaphase onset. The SAC proteins Mad2 and BubR1 target the APC/C activator Cdc20. Mad2 adopts a closed conformation when bound to its kinetochore receptor Mad1 or its target in the checkpoint Cdc20, and an open conformation when unbound to these ligands. The “Mad2 template” of SAC activation predicts that the kinetochore receptor of cytosolic Mad2 is a closed conformer of Mad2 constitutively bound to Mad1, rather than Mad1 itself [...]
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