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Assessment of the Mitotic Spindle Assembly Checkpoint (SAC) as the Target of Anticancer Therapies

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The mitotic spindle assembly checkpoint (SAC) is an essential control system of the eukaryotic cell cycle. This surveillance mechanism monitors the kinetochore, the multi-component complex that assembles on the centromeric DNA and attaches chromosomes to the microtubules of the spindle. The recruitment of mitotic checkpoint proteins to kinetochores that are not correctly attached to microtubules initiates a signalling cascade that results in the CDC20-dependent inhibition of the anaphase-promoting complex/cyclosome (APC/C). Mutations in the genes encoding for diverse SAC proteins have been identified in human tumour cells and associated with chromosome segregation and cancer progression. This work describes the current understanding on the organisation, function and structure of SAC components and shows this knowledge assists the identification of those that may constitute suitable targets for the clinical treatment of cancer.

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Keywords: BUB1/BUBR1; CDC20-MAD2; CENP-E; Mitotic spindle assembly checkpoint (SAC); anticancer therapy; cell cycle; fragment-based screening; genome instability

Document Type: Research Article

Publication date: March 1, 2009

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  • Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
    Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
    As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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