Understanding cytokinesis failure.

Cytokinesis is the final step in cell division. The process begins during chromosome segregation, when the ingressing cleavage furrow begins to partition the cytoplasm between the nascent daughter cells. The process is not completed until much later, however, when the final cytoplasmic bridge connecting the two daughter cells is severed. Cytokinesis is a highly ordered process, requiring an intricate interplay between cytoskeletal, chromosomal and cell cycle regulatory pathways. A surprisingly broad range of additional cellular processes are also important for cytokinesis, including protein and membrane trafficking, lipid metabolism, protein synthesis and signaling pathways. As a highly regulated, complex process, it is not surprising that cytokinesis can sometimes fail. Cytokinesis failure leads to both centrosome amplification and production of tetraploid cells, which may set the stage for the development of tumor cells. However, tetraploid cells are abundant components of some normal tissues including liver and heart, indicating that cytokinesis is physiologically regulated. In this chapter, we summarize our current understanding of the mechanisms of cytokinesis, emphasizing steps in the pathway that may be regulated or prone to failure. Our discussion emphasizes findings in vertebrate cells although we have attempted to highlight important contributions from other model systems.