Analysis of the defects associated with an increase in Aurora B activity during mitosis

Abstract

The cell cycle is a highly regulated process that leads to the duplication of an original cell giving rise to two daughter cells. A key aspect of this process is the faithful duplication of the original genetic material and its subsequent equitable distribution between the daughter cells. To ensure this distribution it is necessary that both sister chromatids from each chromosome attach to microtubules emanating from opposite ends of the spindle (biorientation). Aurora B kinase plays a key role in the establishment of the proper biorientation of sister chromatids during mitosis. Accordingly the absence of Aurora B activity generates massive chromosome segregation problems due to the cells being unable to repair incorrect kinetochore-microtubule attachments. However and remarkably not only the absence of Aurora B but also an increase in its kinase activity is an important threat for cell viability and originates errors during chromosome segregation and cytokinesis. In fact increased levels of this kinase have been associated with different types of cancer and its degree of expression has been related to a worse prognosis. In order to analyse how an increase in Aurora B activity promotes aneuploidy and cancer we have developed a strategy for the identification of mutations that could allow cells to counteract the toxic effects of elevated levels of Aurora B activity. This study could be of pivotal importance to extend our knowledge about the molecular mechanisms by which tumorigenesis processes can be initiated and therefore to help finding possible future cures for this disease.