Mck1 kinase is a new player in the DNA damage checkpoint pathway

Delgado, Nerea Sanvisens; Toczyski, David P.

doi:10.1371/journal.pgen.1008372

Cited by 2 publications

(1 citation statement)

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“…The role of Mck1 in other surveillance mechanisms, like the DNA Damage Checkpoint pathway, Cell Wall Integrity pathway and heat stress response [83] has been characterized earlier. Here we have extended Mck1's function to SPOC/mitotic exit and identified Cdc6 as one Mck1 substrate that regulates SPOC.…”

Section: Discussionmentioning

confidence: 99%

The budding yeast GSK-3 homologue Mck1 is an essential component of the spindle position checkpoint

2022

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The spindle position checkpoint (SPOC) is a mitotic surveillance mechanism in Saccharomyces cerevisiae that prevents cells from completing mitosis in response to spindle misalignment, thereby contributing to genomic integrity. The kinase Kin4, one of the most downstream SPOC components, is essential to stop the mitotic exit network (MEN), a signalling pathway that promotes the exit from mitosis and cell division. Previous work, however, suggested that a Kin4-independent pathway contributes to SPOC, yet the underlying mechanisms remain elusive. Here, we established the glycogen-synthase-kinase-3 (GSK-3) homologue Mck1, as a novel component that works independently of Kin4 to engage SPOC. Our data indicate that both Kin4 and Mck1 work in parallel to counteract MEN activation by the Cdc14 early anaphase release (FEAR) network. We show that Mck1's function in SPOC is mediated by the pre-replication complex protein and mitotic cyclin-dependent kinase (M-Cdk) inhibitor, Cdc6, which is degraded in a Mck1-dependent manner prior to mitosis. Moderate overproduction of Cdc6 phenocopies MCK1 deletion and causes SPOC deficiency via its N-terminal, M-Cdk inhibitory domain. Our data uncover an unprecedented role of GSK-3 kinases in coordinating spindle orientation with cell cycle progression.

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Section: Discussionmentioning

confidence: 99%