Spindle checkpoint-independent inhibition of mitotic chromosome segregation by Drosophila Mps1.

Molecular Biology of the Cell
Friederike AlthoffChristian F Lehner

Abstract

Monopolar spindle 1 (Mps1) is essential for the spindle assembly checkpoint (SAC), which prevents anaphase onset in the presence of misaligned chromosomes. Moreover, Mps1 kinase contributes in a SAC-independent manner to the correction of erroneous initial attachments of chromosomes to the spindle. Our characterization of the Drosophila homologue reveals yet another SAC-independent role. As in yeast, modest overexpression of Drosophila Mps1 is sufficient to delay progression through mitosis during metaphase, even though chromosome congression and metaphase alignment do not appear to be affected. This delay in metaphase depends on the SAC component Mad2. Although Mps1 overexpression in mad2 mutants no longer causes a metaphase delay, it perturbs anaphase. Sister kinetochores barely move apart toward spindle poles. However, kinetochore movements can be restored experimentally by separase-independent resolution of sister chromatid cohesion. We propose therefore that Mps1 inhibits sister chromatid separation in a SAC-independent manner. Moreover, we report unexpected results concerning the requirement of Mps1 dimerization and kinase activity for its kinetochore localization in Drosophila. These findings further expand Mps1's signif...Continue Reading

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Citations

Jun 30, 2015·Cell Reports·Conrad von SchubertErich A Nigg
Aug 18, 2012·Developmental Cell·Mathijs VleugelGeert J P L Kops
May 10, 2016·ELife·Benjamin M Stormo, Donald T Fox
Jun 11, 2016·PloS One·Xiao-Qin HeHai-Long Wang
Jan 28, 2015·Journal of Breath Research·Mihály BorosAnton Amann
Jan 9, 2020·The Journal of Cell Biology·Sofia Cunha-SilvaCarlos Conde
Feb 8, 2019·Cell Cycle·Zi-Yun YiWei-Ping Qian
Apr 5, 2018·Journal of Developmental Biology·Giuliana D ClementeHans-Arno J Müller
Nov 22, 2013·Biochemical Society Transactions·Silke Hauf

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Methods Mentioned

BETA
transgenic
immunoprecipitation
coimmunoprecipitation
immunodepletion
PCR
transfection

Software Mentioned

Huygens Remote Manager
ImageJ
Photoshop
Imaris

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