Toward a systems-level view of mitotic checkpoints.
Reproduction and natural selection are the key elements of life. In order to reproduce, the genetic material must be doubled, separated and placed into two new daughter cells, each containing a complete set of chromosomes and organelles. In mitosis, transition from one process to the next is guided by intricate surveillance mechanisms, known as the mitotic checkpoints. Dis-regulation of cell division through checkpoint malfunction can lead to developmental defects and contribute to the development or progression of tumors. This review approaches two important mitotic checkpoints, the spindle assembly checkpoint (SAC) and the spindle position checkpoint (SPOC). The highly conserved spindle assembly checkpoint (SAC) controls the onset of anaphase by preventing premature segregation of the sister chromatids of the duplicated genome, to the spindle poles. In contrast, the spindle position checkpoint (SPOC), in the budding yeast Saccharomyces cerevisiae, ensures that during asymmetric cell division mitotic exit does not occur until the spindle is properly aligned with the cell polarity axis. Although there are no known homologs, there is indication that functionally similar checkpoints exist also in animal cells. This review can be regarded as an "executable model", which could be easily translated into various quantitative concrete models like Petri nets, ODEs, PDEs, or stochastic particle simulations. It can also function as a base for developing quantitative models explaining the interplay of the various components and proteins controlling mitosis.
Bio System Analysis Group, Friedrich-Schiller-University Jena, and Jena Centre for Bioinformatics (JCB), 07743 Jena, Germany; Umm Al-Qura University, 1109 Makkah, Saudi Arabia; Al-Qunfudah Center for Scientific Research (QCSR), 21912 Al-Qunfudah, Saudi Arabia. Electronic address: bashar.ibrahim@uni-jena.de.
Bashar
B
Ibrahim
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D006801:Humans; D018386:Kinetochores / Q000502:physiology*; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics*; D008957:Models, Genetic; D015398:Signal Transduction / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics*; D049490:Systems Biology / Q000379:methods
D018797:Cell Cycle Proteins; D004247:DNA
Kinetochore; Spindle assembly checkpoint; Spindle position checkpoint; Systems biology