RT Journal Article
SR Electronic
T1 Interactions between N-Terminal Modules in MPS1 Enable Spindle Checkpoint Silencing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 438903
DO 10.1101/438903
A1 Spyridon T. Pachis
A1 Yoshitaka Hiruma
A1 Anastassis Perrakis
A1 Geert J.P.L. Kops
YR 2018
UL http://biorxiv.org/content/early/2018/10/10/438903.abstract
AB Faithful chromosome segregation relies on the ability of the spindle assembly checkpoint (SAC) to delay anaphase onset until all chromosomes are attached to the mitotic spindle via their kinetochores. MPS1 kinase is recruited to unattached kinetochores to initiate SAC signaling, and is removed from kinetochores once stable microtubule attachments have been formed to allow normal mitotic progression. Here we show that a helical fragment within the kinetochore-targeting NTE module of MPS1 is required for interactions with kinetochores, and also forms intramolecular interactions with its adjacent TPR domain. Bypassing this NTE-TPR interaction results in high MPS1 levels at kinetochores due to loss of regulatory input into MPS1 localization, ineffecient MPS1 delocalization from kinetochores upon microtubule attachment, and SAC silencing defects. These results show that SAC responsiveness to attachments relies on regulated intramolecular interactions in MPS1 and highlight the sensitivity of mitosis to perturbations in the dynamics of the MSP1-NDC80-C interactions.