How chromosome mis-segregation leads to cancer: lessons from BubR1 mouse models

Abstract

Alteration in chromosome numbers and structures instigate and foster massive genetic instability. As Boveri has seen a hundred years ago (Boveri, 1914; 2008), aneuploidy is hallmark of many cancers. However, whether aneuploidy is the cause or the result of cancer is still at debate. The molecular mechanism behind aneuploidy includes the chromo-some mis-segregation in mitosis by the compromise of spindle assembly checkpoint (SAC). SAC is an elaborate network of proteins, which monitor that all chromosomes are bipolarly attached with the spindles. Therefore, the weakening of the SAC is the major reason for chromosome number instability, while complete compromise of SAC results in detrimental death, exemplified in natural abortion in embryonic stage. Here, I will review on the recent progress on the understanding of chromosome mis-segregation and cancer, based on the comparison of different mouse models of BubR1, the core component of SAC.

Keywords: BubR1; BubR1 acetylation; aneuploidy; cancer; chromosome mis-segregation; mouse.

Fig. 1.

Schematic illustration of human BubR1 and its ortholgue yeast Mad3. Functional domains, suggested functions, and reported phosphorylation and acetylation sites are marked.