Mps1 promotes chromosome meiotic chromosome biorientation through Dam1

Meyer, Régis E.; Brown, Jamin; Beck, Lindsay; Dawson, Dean

doi:10.1091/mbc.e17-08-0503

Cited by 17 publications

(24 citation statements)

References 67 publications

(87 reference statements)

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“…4 C). Representative traces of the GFP-tagged centromeres in a wild-type cell, a dam1-md mutant (which is defective in maintaining end-on kinetochore attachments; (Meyer et al, 2018)) and three mps1-R170S cells show that in the mps1-R170S mutants the centromeres appear locked-in-place (Fig. 4C).…”

Section: Resultsmentioning

confidence: 99%

“…The failure of MPS1 mutants to phosphorylate Dam1 does not explain the massive defects in meiotic chromosome segregation exhibited by MPS1 mutants. Despite their defects in kMT interactions, dam1-2A mutants that cannot be phosphorylated by Mps1 exhibit rather mild meiotic chromosome segregation defects (Shimogawa et al, 2006; Meyer et al, 2018). Thus, there must be another role (or roles) of Mps1 that explains its essentiality for meiotic chromosome segregation.…”

Section: Discussionmentioning

confidence: 99%

“…These pauses could represent losses of kinetochore microtubule plus-end attachment or pauses in microtubule depolymerization, or both. Given that phosphorylation of Dam1 by Mps1 strengthens kinetochore attachments to plus ends (Shimogawa et al, 2006; Meyer et al, 2018) some of the pauses in MPS1 mutants are probably due to failures in maintaining the kinetochore-plus-end connection. However, other results suggest that this is not the major defect.…”

Section: Discussionmentioning

confidence: 99%

“…However, other results suggest that this is not the major defect. First, MPS1 mutants exhibit low levels of the lagging chromosomes that are an indicator of a defect in attaching kinetochores to microtubules (Meyer et al, 2018; 2013). Second, MPS1 mutants exhibit a stuck-in-the-middle phenotype in which kinetochores maintain a very stable position in mid-spindle.…”

Section: Discussionmentioning

confidence: 99%

“…PCR-based methods were used to create complete deletions of ORFs and promoter insertions (Janke et al, 2004; Longtine et al, 1998). spo11::KANMX, spo11::HIS3MX6, P GPD1 -GAL4(848)-ER-URA3::hphNT1, natNT2::P GAL1 -NDT80 , KANMX::P GAL1 -NDT80, mps1::KANMX, TRP1::10Xmyc-mps1-as1 (=mps1-as1), mps1-R170S::his5, KANMX::P CLB2 -3HA-MPS1 (=mps1-md) , KANMX::P CLB2 -3HA-NDC80 (=ndc80-md), KANMX::P CLB2 -3HA-DAM1 (=dam1-md), SPC42-DsRed-URA3 strains were generated previously (Meyer et al, 2018; 2013). The mEos2-TUB1 strains were generated by inserting pHIS3p:mEos2-Tub1+3’UTR::TRP1 plasmid (https://www.addgene.org/50652/) in the TUB1 locus as described (Markus et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

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Mps1 promotes poleward chromosome movements in meiotic pro-metaphase

Meyer

Tipton

Gorbsky

et al. 2020

Preprint

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ABSTRACTIn prophase of meiosis I, homologous partner chromosomes pair and become connected by crossovers. Chiasmata, the connections formed between the partners enable the chromosome pair, called a bivalent to attach as a single unit to the spindle. When the meiosis I spindle forms, most bivalents are associated with a single spindle pole and go through a series of oscillations on the spindle attaching and detaching from microtubules until the partners of the bivalent are bi-oriented, that is, attached to microtubules from opposite sides of the spindle, and prepared to be segregated at anaphase I. The conserved, kinetochore-associated kinase, Mps1, is essential for the bivalents to be pulled by microtubules across the spindle. Here we explore the role of Mps1 in this process. In MPS1 mutants, kinetochores can attach to microtubules and, when they are pulled by microtubule de-polymerization, can move at normal speeds across the spindle. In MPS1 mutants, kinetochores often become locked-in-place on the pro-metaphase spindle and pro-metaphase kinetochore microtubules reduced turnover. Together the results suggest that Mps1 is necessary to promote depolymerization of kinetochore-microtubules during the bi-orientation process.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Mps1 promotes poleward chromosome movements in meiotic pro-metaphase

Meyer

Tipton

Gorbsky

et al. 2020

Preprint

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Mps1 controls spindle assembly, SAC, and DNA repair in the first cleavage of mouse early embryos

Pan

et al. 2020

J of Cellular Biochemistry

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Monopolar spindle-1 (Mps1) is a critical interphase regulator that also involves into the spindle assembly checkpoint for the cell cycle control in both mitosis and meiosis. However, the functions of Mps1 during mouse early embryo development is still unclear. In this study, we reported the important roles of Mps1 in the first cleavage of mouse embryos. Our data indicated that the loss of Mps1 activity caused precocious cleavage of zygotes to 2-cell embryos; however, prolonged culture disturbed the early embryo development to the blastocyst. We found that the spindle organization was disrupted after Mps1 inhibition, and the chromosomes were misaligned in the first cleavage. Moreover, the kinetochore-microtubule attachment was lost and Aurora B failed to accumulate to the kinetochores, indicating that the spindle assembly checkpoint (SAC) was activated. Furthermore, the inhibition of Mps1 activity resulted in an increase of DNA damage, which further induced oxidative stress, showing with positive γ-H2A.X signal and increased reactive oxygen species level. Ultimately, irreparable DNA damage and oxidative stressactivated apoptosis and autophagy, which was confirmed by the positive Annexin-V signal and increased autophagosomes. Taken together, our data indicated that Mps1 played important roles in the control of SAC and DNA repair during mouse early embryo development.

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Meiotic regulation of the Ndc80 complex composition and function

Chen

Ünal

2021

Curr Genet

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This review describes the current models for how the subunit abundance of the Ndc80 complex, a key kinetochore component, is regulated in budding yeast and metazoan meiosis. The past decades of kinetochore research have established the Ndc80 complex to be a key microtubule interactor and a central hub for regulating chromosome segregation. Recent studies further demonstrate that Ndc80 is the limiting kinetochore subunit that dictates the timing of kinetochore activation in budding yeast meiosis. Here, we discuss the molecular circuits that regulate Ndc80 protein synthesis and degradation in budding yeast meiosis and compare the findings with those from metazoans. We envision the regulatory principles discovered in budding yeast to be conserved in metazoans, thereby providing guidance into future investigations on kinetochore regulation in human health and disease.

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Mps1 promotes chromosome meiotic chromosome biorientation through Dam1

Cited by 17 publications

References 67 publications

Mps1 promotes poleward chromosome movements in meiotic pro-metaphase

Mps1 promotes poleward chromosome movements in meiotic pro-metaphase

Mps1 controls spindle assembly, SAC, and DNA repair in the first cleavage of mouse early embryos

Meiotic regulation of the Ndc80 complex composition and function

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