May 5, 2011

So much depends on healthy cell division, so it is no wonder how magnificent the spindle checkpoint is. This checkpoint keeps our cells healthy and our biologists busy as they try to figure it all out.

The spindle checkpoint ensures that a dividing cell undergoes anaphase only when all chromosomes are properly attached the mitotic spindle. Without this checkpoint, cells may end up with an incorrect number of chromosomes. Recently, a group teased apart some of the specifics of the checkpoint by using a construct engineered in the lab. This construct fused the kinetochore protein Mis12 to the checkpoint protein Mad1, which blocks progression to anaphase when it localizes to kinetochores not attached to the spindle. This Mad1-Mis12 construct targeted Mad1 to kinetochores despite their orientation state on the mitotic spindle, meaning that this construct allowed researchers to distinguish between Mad1 checkpoint signaling and the initial orientation error signal. The images above show metaphase spindles in control cells (top) or cells with the Mad1-Mis12 construct (bottom). The construct (mCherry, red in merged image) localizes to kinetochores (CREST, blue in merged) attached to the spindle (tubulin, green).

Maldonado, M., & Kapoor, T. (2011). Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation Nature Cell Biology, 13 (4), 475-482 DOI: 10.1038/ncb2223
Adapted by permission from Macmillan Publishers Ltd, copyright 2011