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@ARTICLE{Rathi:182432,
author = {S. Rathi and I. Polat and G. Pereira$^*$},
title = {{T}he budding yeast {GSK}-3 homologue {M}ck1 is an
essential component of the spindle position checkpoint.},
journal = {Open biology},
volume = {12},
number = {11},
issn = {2046-2441},
address = {London},
publisher = {Royal Society Publishing},
reportid = {DKFZ-2022-02641},
pages = {220203},
year = {2022},
note = {DKFZ-ZMBH Alliance / #LA:A180#},
abstract = {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.},
keywords = {Humans / Saccharomyces cerevisiae Proteins: genetics /
Glycogen Synthase Kinase 3: genetics / Glycogen Synthase
Kinase 3: metabolism / Spindle Apparatus: metabolism /
Saccharomycetales: metabolism / Protein Serine-Threonine
Kinases / Phosphorylation / Saccharomyces cerevisiae:
genetics / Mitosis / Cell Cycle Proteins: metabolism /
Protein Tyrosine Phosphatases: genetics / Protein Tyrosine
Phosphatases: metabolism / Cdc6 (Other) / MCK1 (Other) /
budding yeast (Other) / cell division (Other) / checkpoint
control (Other) / mitotic exit (Other) / Saccharomyces
cerevisiae Proteins (NLM Chemicals) / Glycogen Synthase
Kinase 3 (NLM Chemicals) / Protein Serine-Threonine Kinases
(NLM Chemicals) / Cell Cycle Proteins (NLM Chemicals) /
CDC14 protein, S cerevisiae (NLM Chemicals) / Protein
Tyrosine Phosphatases (NLM Chemicals) / MCK1 protein, S
cerevisiae (NLM Chemicals)},
cin = {A180},
ddc = {570},
cid = {I:(DE-He78)A180-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36321416},
doi = {10.1098/rsob.220203},
url = {https://inrepo02.dkfz.de/record/182432},
}