Some authors have demonstrated that cells with compromised (or weakened) checkpoint machinery can progress to anaphase with one or more chromosomes unattached to microtubules, and these cells can arrest in the cell cycle but eventually finish the cell cycle, generating aneuploid cells [32], [33].
Two of the causes of CIN are weakened mitotic checkpoint signaling and persistent merotelic attachments that result in lagging chromosomes during anaphase.
Mps1 activity is indispensable for cell viability, but viability is maintained in CIN tumor cells that have a weakened mitotic checkpoint [5].
Reduced Mps1 kinase activity allows weakened mitotic checkpoint signaling as well as lagging chromosomes at anaphase, two major defects suggested to contribute to CIN in tumor cells [5], [10].
They are able to survive and proliferate because key checkpoints are weakened, thereby increasing the barrier for activation of DDR signalling [ 4].
Conversely, MAD2 decreased significatively in the Myc cells treated with PTX, suggesting that the overexpression of Myc may weaken the mitotic checkpoint.
Therefore, it is possible that, as the DNA damage checkpoint weakens, the kinase may overcome the arrest.
In theory these activities can be quickly elevated with the weakening of checkpoint signals, leading to further deactivation of checkpoint signals, and eventually mitotic reentry.
