Figure 6

The many roles of Mps1 in the maintenance of genomic integrity. Many functions for hMps1 have been described in human cells, in both the centriole and nuclear cycles. Although the described functions for hMps1 are quite varied, when properly coordinated they ensure the integrity of the genome. Recent work discussed extensively in this review suggests that hMps1 functions in both procentriole assembly and centriole maturation. While it is possible that these functions are dispensable, failure to properly regulate them leads to centriole overproduction that can generate aberrant mitotic spindles. hMps1 has also been implicated in cytokinesis [59], responsible for partitioning of one copy each of the duplicated genome and centrosome into daughter cells. hMps1 regulates the p53-dependent post-mitotic checkpoint that prevents cell cycle entry after failed mitosis, and defects in this function can allow aneuploid cells to proliferate [57]. hMps1 regulates the Chk2-dependent DNA damage response, and defects in this function lead to defective arrest in the presence of damaged DNA [58]. Finally, hMps1 regulates the spindle assembly checkpoint [55], and defects in this function lead to chromosome segregation errors. The function of hMps1 in SMAD signaling represents a transcriptional input into the spindle assembly checkpoint [56]. In this figure, a circle represents the cell cycle, with phases labeled and arrows representing transitions. The centriole cycle is depicted on the inside, with carets indicating centriolar appendages (which are assembled onto the two oldest centrioles during mitosis) and cartwheels (which are degraded during mitosis) as in Figures 1, 3, and 4. The nuclear cycle is depicted on the outside, with the nucleus as a grey oval, and chromosomes in blue. The mitotic spindle is indicated by green lines representing microtubules, mitotic chromosomes in blue, kinetochores in cyan, and red lines indicating an activated spindle checkpoint.