共 103 条
A common molecular mechanism underlies the role of Mps1 in chromosome biorientation and the spindle assembly checkpoint
被引:23
作者:
Benzi, Giorgia
[1
]
Camasses, Alain
[2
]
Atsunori, Yoshimura
[3
]
Katou, Yuki
[3
]
Shirahige, Katsuhiko
[3
]
Piatti, Simonetta
[1
]
机构:
[1] Univ Montpellier, CNRS, CRBM, Montpellier, France
[2] Univ Montpellier, CNRS, IGMM, Montpellier, France
[3] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan
关键词:
chromosome biorientation;
error correction;
Mps1;
Spc105;
spindle assembly checkpoint;
AURORA-B KINASE;
KINETOCHORE-MICROTUBULE ATTACHMENT;
SISTER-CHROMATID SEPARATION;
DUPLICATION GENE MPS1;
PROTEIN PHOSPHATASE 1;
SACCHAROMYCES-CEREVISIAE;
BUDDING YEAST;
OUTER KINETOCHORE;
ERROR-CORRECTION;
PHOSPHORYLATION;
D O I:
10.15252/embr.202050257
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The Mps1 kinase corrects improper kinetochore-microtubule attachments, thereby ensuring chromosome biorientation. Yet, its critical phosphorylation targets in this process remain largely elusive. Mps1 also controls the spindle assembly checkpoint (SAC), which halts chromosome segregation until biorientation is attained. Its role in SAC activation is antagonised by the PP1 phosphatase and involves phosphorylation of the kinetochore scaffold Knl1/Spc105, which in turn recruits the Bub1 kinase to promote assembly of SAC effector complexes. A crucial question is whether error correction and SAC activation are part of a single or separable pathways. Here, we isolate and characterise a new yeast mutant, mps1-3, that is severely defective in chromosome biorientation and SAC signalling. Through an unbiased screen for extragenic suppressors, we found that mutations lowering PP1 levels at Spc105 or forced association of Bub1 with Spc105 reinstate both chromosome biorientation and SAC signalling in mps1-3 cells. Our data argue that a common mechanism based on Knl1/Spc105 phosphorylation is critical for Mps1 function in error correction and SAC signalling, thus supporting the idea that a single sensory apparatus simultaneously elicits both pathways.
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页数:20
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