Biology subjects

Barr, F. A.

Publications and source records attributed to Barr, F. A..

2 recordsLinked to original sources

bioRxiv2019

Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A

Aurora kinases create phosphorylation gradients within the spindle during prometaphase and anaphase. These locally regulate factors that promote spindle organisation, chromosome condensation and movement, and cytokinesis. We show that one such factor is the kinesin KIF4A, which is present along the chromosome axes throughout mitosis and the central spindle in anaphase. These two pools of KIF4A depend on condensin I and PRC1, respectively. Previous work has shown KIF4A is activated by Aurora B at the anaphase central spindle. However, whether or not chromosome-associated KIF4A bound to condensin I is regulated by Aurora kinases remain unclear. To determine the roles of the two different pools of KIF4A, we generated specific point mutants that are unable to interact with either condensin I or PRC1, or are deficient for Aurora kinase regulation. By analysing these mutants, we show that Aurora kinases phosphorylate the condensin I dependent pool of KIF4A and thus actively promote chromosome congression from the spindle poles to the metaphase plate.

cell biology↗

bioRxiv2019

Checkpoint signaling and error correction require regulation of the MPS1 T-loop by PP2A-B56

During mitosis, the formation of microtubule-kinetochore attachments is monitored by the serine/threonine kinase Mono-Polar Spindle 1 (MPS1). MPS1 is recruited to unattached kinetochores where it phosphorylates KNL1, BUB1 and MAD1 to initiate the spindle checkpoint. This arrests the cell cycle until all kinetochores have been stably captured by microtubules. MPS1 also contributes to the error correction process rectifying incorrect kinetochore attachments. MPS1 activity at kinetochores requires auto-phosphorylation at multiple sites including T676 in the activation segment or \"T-loop\". We now demonstrate that a BUBR1-bound pool of PP2A-B56 regulates MPS1 T-loop autophosphorylation and hence activation status in mammalian cells. Overriding this regulation using phospho-mimetic mutations in the MPS1 T-loop to generate a constitutively active kinase results in a prolonged mitotic arrest with continuous turn-over of microtubule-kinetochore attachments. Dynamic regulation of MPS1 catalytic activity by kinetochore-localized PP2A-B56 is thus critical for controlled MPS1 activity and timely cell cycle progression.

cell biology↗