Newly identified roles for an old guardian: profound deficiency of the mitotic spindle checkpoint protein BubR1 leads to early aging and infertility.
The mitotic spindle checkpoint ensures proper chromosome segregation, and thereby guards against the deleterious effects of aneuploidy. The protein components of the check-point 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 aging and infertility.
Kim
Mijin
M
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Kao
Gary D
GD
D000375:Aging / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D006801:Humans; D007246:Infertility / Q000378:metabolism*; D011494:Protein Kinases / Q000172:deficiency*; D017346:Protein Serine-Threonine Kinases; D008941:Spindle Apparatus
C584278:Bub1b protein, mouse; D018797:Cell Cycle Proteins; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases