Newly identified roles for an old guardian: Profound deficiency of the mitotic spindle checkpoint protein BubR1 leads to early aging and infertility

Abstract

The mitotic spindle checkpoint ensures proper chromosome segregation, and thereby guards against the deleterious effects of aneuploidy. The protein components of the checkpoint machinery include evolutionarily conserved proteins such as BubR1. While the molecular and cellular biology of this checkpoint is becoming increasingly clarified, the ultimate consequences for overall health of deficiency of specific components such as BubR1 are much less clear–in part due to the embryonic lethality of complete knockouts. Through a clever combination of hypomorphic and knockout alleles, Baker and colleagues were able to engineer mice with graduated levels of BubR1 protein. In doing so, they established the threshold permitting survival to adulthood, but even more intriguingly, they discovered critical roles for BubR1 in preventing early ageing and infertility