scholarly journals Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I

2013 ◽  
Vol 202 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Olga Davydenko ◽  
Richard M. Schultz ◽  
Michael A. Lampson
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Partial Reduction ◽  
Slow Increase ◽  
Spindle Formation ◽  
Bipolar Spindle ◽  
Nuclear Envelope Breakdown ◽  
Spindle Microtubules ◽  
Meiosis I

Chromosome segregation during cell division depends on stable attachment of kinetochores to spindle microtubules. Mitotic spindle formation and kinetochore–microtubule (K-MT) capture typically occur within minutes of nuclear envelope breakdown. In contrast, during meiosis I in mouse oocytes, formation of the acentrosomal bipolar spindle takes 3–4 h, and stabilization of K-MT attachments is delayed an additional 3–4 h. The mechanism responsible for this delay, which likely prevents stabilization of erroneous attachments during spindle formation, is unknown. Here we show that during meiosis I, attachments are regulated by CDK1 activity, which gradually increases through prometaphase and metaphase I. Partial reduction of CDK1 activity delayed formation of stable attachments, whereas a premature increase in CDK1 activity led to precocious formation of stable attachments and eventually lagging chromosomes at anaphase I. These results indicate that the slow increase in CDK1 activity in meiosis I acts as a timing mechanism to allow stable K-MT attachments only after bipolar spindle formation, thus preventing attachment errors.

scholarly journals PLK1 is required for chromosome compaction and microtubule organization in mouse oocytes

2020 ◽  
Vol 31 (12) ◽  
pp. 1206-1217
Author(s):  
Tara M. Little ◽  
Philip W. Jordan
Keyword(s):  
Chromosome Segregation ◽  
Microtubule Organizing Center ◽  
Microtubule Organization ◽  
Spindle Formation ◽  
Bipolar Spindle ◽  
Mouse Oocytes ◽  
Organizing Center ◽  
Meiosis I

By deleting Plk1 in mouse oocytes before meiotic resumption, we show that PLK1 is essential for the formation of condensed bivalent chromosomes, microtubule organizing center fragmentation, liquid-like spindle domain localization, and bipolar spindle formation. Thus, PLK1 coordinates processes that ensure chromosome segregation during meiosis I.

scholarly journals Paired arrangement of kinetochores together with microtubule pivoting and dynamics drive kinetochore capture in meiosis I

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Gheorghe Cojoc ◽  
Ana-Maria Florescu ◽  
Alexander Krull ◽  
Anna H. Klemm ◽  
Nenad Pavin ◽  
...  
Keyword(s):  
Cell Division ◽  
Fission Yeast ◽  
General Feature ◽  
Protein Complexes ◽  
Spindle Pole ◽  
Single Object ◽  
Homologous Chromosomes ◽  
Angular Movement ◽  
Spindle Microtubules ◽  
Meiosis I

Abstract Kinetochores are protein complexes on the chromosomes, whose function as linkers between spindle microtubules and chromosomes is crucial for proper cell division. The mechanisms that facilitate kinetochore capture by microtubules are still unclear. In the present study, we combine experiments and theory to explore the mechanisms of kinetochore capture at the onset of meiosis I in fission yeast. We show that kinetochores on homologous chromosomes move together, microtubules are dynamic and pivot around the spindle pole, and the average capture time is 3–4 minutes. Our theory describes paired kinetochores on homologous chromosomes as a single object, as well as angular movement of microtubules and their dynamics. For the experimentally measured parameters, the model reproduces the measured capture kinetics and shows that the paired configuration of kinetochores accelerates capture, whereas microtubule pivoting and dynamics have a smaller contribution. Kinetochore pairing may be a general feature that increases capture efficiency in meiotic cells.

scholarly journals Increased Expression of Maturation Promoting Factor Components Speeds Up Meiosis in Oocytes from Aged Females

2018 ◽  
Vol 19 (9) ◽  
pp. 2841 ◽  
Author(s):  
Marketa Koncicka ◽  
Anna Tetkova ◽  
Denisa Jansova ◽  
Edgar Del Llano ◽  
Lenka Gahurova ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Maternal Age ◽  
Germ Line ◽  
Nuclear Lamina ◽  
Nuclear Envelope Breakdown ◽  
Meiotic Progression ◽  
Translational Activity ◽  
Female Germ Line ◽  
Mammalian Female ◽  
Meiosis I

The rate of chromosome segregation errors that emerge during meiosis I in the mammalian female germ line are known to increase with maternal age; however, little is known about the underlying molecular mechanism. The objective of this study was to analyze meiotic progression of mouse oocytes in relation to maternal age. Using the mouse as a model system, we analyzed the timing of nuclear envelope breakdown and the morphology of the nuclear lamina of oocytes obtained from young (2 months old) and aged females (12 months old). Oocytes obtained from older females display a significantly faster progression through meiosis I compared to the ones obtained from younger females. Furthermore, in oocytes from aged females, lamin A/C structures exhibit rapid phosphorylation and dissociation. Additionally, we also found an increased abundance of MPF components and increased translation of factors controlling translational activity in the oocytes of aged females. In conclusion, the elevated MPF activity observed in aged female oocytes affects precocious meiotic processes that can multifactorially contribute to chromosomal errors in meiosis I.

Regulation of Microtubule Assembly: The View From The End

2000 ◽  
Vol 6 (S2) ◽  
pp. 80-81
Author(s):  
L. Cassimeris ◽  
C. Spittle ◽  
M. Kratzer
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Dynamic Instability ◽  
Intrinsic Property ◽  
Microtubule Dynamics ◽  
Microtubule Assembly ◽  
Chromosome Movement ◽  
Spindle Formation ◽  
Associated Proteins

The mitotic spindle is responsible for chromosome movement during mitosis. It is composed of a dynamic array of microtubules and associated proteins whose assembly and constant turnover are required for both spindle formation and chromosome movement. Because microtubule assembly and turnover are necessary for chromosome segregation, we are studying how cells regulate microtubule dynamics. Microtubules are polarized polymers composed of tubulin subunits; they assemble by a process of dynamic instability where individual microtubules exist in persistent phases of elongation or rapid shortening with abrupt transitions between these two states. The switch from elongation to shortening is termed catastrophe, and the switch from shortening to elongation, rescue. Although dynamic instability is an intrinsic property of the tubulin subunits, cells use associated proteins to both speed elongation (∼ 10 fold) and regulate transitions.The only protein isolated to date capable of promoting fast polymerization consistent with rates in vivo is XMAP215, a 215 kD protein from Xenopus eggs.

scholarly journals csi2p modulates microtubule dynamics and organizes the bipolar spindle for chromosome segregation

2014 ◽  
Vol 25 (24) ◽  
pp. 3900-3908 ◽  
Author(s):  
Judite Costa ◽  
Chuanhai Fu ◽  
V. Mohini Khare ◽  
Phong T. Tran
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Microtubule Dynamics ◽  
High Rate ◽  
Spindle Formation ◽  
Bipolar Spindle ◽  
Eukaryotic Chromosome ◽  
Relative Contribution ◽  
Multiple Phenotypes

Proper chromosome segregation is of paramount importance for proper genetic inheritance. Defects in chromosome segregation can lead to aneuploidy, which is a hallmark of cancer cells. Eukaryotic chromosome segregation is accomplished by the bipolar spindle. Additional mechanisms, such as the spindle assembly checkpoint and centromere positioning, further help to ensure complete segregation fidelity. Here we present the fission yeast csi2+. csi2p localizes to the spindle poles, where it regulates mitotic microtubule dynamics, bipolar spindle formation, and subsequent chromosome segregation. csi2 deletion (csi2Δ) results in abnormally long mitotic microtubules, high rate of transient monopolar spindles, and subsequent high rate of chromosome segregation defects. Because csi2Δ has multiple phenotypes, it enables estimates of the relative contribution of the different mechanisms to the overall chromosome segregation process. Centromere positioning, microtubule dynamics, and bipolar spindle formation can all contribute to chromosome segregation. However, the major determinant of chromosome segregation defects in fission yeast may be microtubule dynamic defects.

scholarly journals The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation

2006 ◽  
Vol 173 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Susan L. Kline ◽  
Iain M. Cheeseman ◽  
Tetsuya Hori ◽  
Tatsuo Fukagawa ◽  
Arshad Desai
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Essential Role ◽  
Stable Complex ◽  
Wild Type ◽  
Outer Plate ◽  
Checkpoint Protein ◽  
Kinetochore Assembly ◽  
Attachment Sites ◽  
Spindle Microtubules

During cell division, kinetochores form the primary chromosomal attachment sites for spindle microtubules. We previously identified a network of 10 interacting kinetochore proteins conserved between Caenorhabditis elegans and humans. In this study, we investigate three proteins in the human network (hDsn1Q9H410, hNnf1PMF1, and hNsl1DC31). Using coexpression in bacteria and fractionation of mitotic extracts, we demonstrate that these proteins form a stable complex with the conserved kinetochore component hMis12. Human or chicken cells depleted of Mis12 complex subunits are delayed in mitosis with misaligned chromosomes and defects in chromosome biorientation. Aligned chromosomes exhibited reduced centromere stretch and diminished kinetochore microtubule bundles. Consistent with this, localization of the outer plate constituent Ndc80HEC1 was severely reduced. The checkpoint protein BubR1, the fibrous corona component centromere protein (CENP) E, and the inner kinetochore proteins CENP-A and CENP-H also failed to accumulate to wild-type levels in depleted cells. These results indicate that a four-subunit Mis12 complex plays an essential role in chromosome segregation in vertebrates and contributes to mitotic kinetochore assembly.

scholarly journals Reductionism at the vertebrate kinetochore

2012 ◽  
Vol 200 (1) ◽  
pp. 7-8 ◽  
Author(s):  
Ana Stankovic ◽  
Lars E.T. Jansen
Keyword(s):  
Chromosome Segregation ◽  
Protein Interactions ◽  
Mitotic Spindle ◽  
De Novo ◽  
Large Structure ◽  
Cell Biol ◽  
Spindle Microtubules ◽  
The Creation

The kinetochore forms the site of attachment for mitotic spindle microtubules driving chromosome segregation. The interdependent protein interactions in this large structure have made it difficult to dissect the function of its components. In this issue, Hori et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201210106) present a novel and powerful methodology to address the sufficiency of individual proteins for the creation of a functional de novo centromere.

scholarly journals Cohesins Determine the Attachment Manner of Kinetochores to Spindle Microtubules at Meiosis I in Fission Yeast

2003 ◽  
Vol 23 (11) ◽  
pp. 3965-3973 ◽  
Author(s):  
Shihori Yokobayashi ◽  
Masayuki Yamamoto ◽  
Yoshinori Watanabe
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Specific Requirement ◽  
Spindle Poles ◽  
Chromatid Cohesion ◽  
Spindle Microtubules ◽  
Yeast Meiosis ◽  
Meiosis I ◽  
Random Division

ABSTRACT During mitosis, sister kinetochores attach to microtubules that extend to opposite spindle poles (bipolar attachment) and pull the chromatids apart at anaphase (equational segregation). A multisubunit complex called cohesin, including Rad21/Scc1, plays a crucial role in sister chromatid cohesion and equational segregation at mitosis. Meiosis I differs from mitosis in having a reductional pattern of chromosome segregation, in which sister kinetochores are attached to the same spindle (monopolar attachment). During meiosis, Rad21/Scc1 is largely replaced by its meiotic counterpart, Rec8. If Rec8 is inactivated in fission yeast, meiosis I is shifted from reductional to equational division. However, the reason rec8Δ cells undergo equational rather than random division has not been clarified; therefore, it has been unclear whether equational segregation is due to a loss of cohesin in general or to a loss of a specific requirement for Rec8. We report here that the equational segregation at meiosis I depends on substitutive Rad21, which relocates to the centromeres if Rec8 is absent. Moreover, we demonstrate that even if sufficient amounts of Rad21 are transferred to the centromeres at meiosis I, thereby establishing cohesion at the centromeres, rec8Δ cells never recover monopolar attachment but instead secure bipolar attachment. Thus, Rec8 and Rad21 define monopolar and bipolar attachment, respectively, at meiosis I. We conclude that cohesin is a crucial determinant of the attachment manner of kinetochores to the spindle microtubules at meiosis I in fission yeast.

scholarly journals Modeling reveals cortical dynein-dependent oscillations in bipolar spindle length

2020 ◽  
Author(s):  
Dayna Mercadante ◽  
Amity Manning ◽  
Sarah Olson
Keyword(s):  
Experimental Data ◽  
Mitotic Spindle ◽  
Force Generation ◽  
Mitotic Progression ◽  
Computational Framework ◽  
Spindle Formation ◽  
Bipolar Spindle ◽  
Spindle Dynamics ◽  
Force Components ◽  
Over Time

AbstractProper formation and maintenance of the mitotic spindle is required for faithful cell division. While much work has been done to understand the roles of the key force components of the mitotic spindle, identifying the consequences of force perturbations in the spindle remains a challenge. We develop a computational framework accounting for the minimal force requirements of mitotic progression. To reflect early spindle formation, we account for microtubule dynamics and interactions with major force-generating motors, excluding chromosome interactions that dominate later in mitosis. We directly integrate our experimental data to define and validate the model, and then use simulations to analyze individual force components over time and their relationship to spindle dynamics, making it distinct from previously published models. Rather than achieving and maintaining a constant bipolar spindle length, oscillations in pole to pole distance occur that coincide with microtubule binding and force generation by cortical dynein. In the context of high kinesin-14 (HSET) activity, we identify the requirement of high cortical dynein activity for bipolar spindle formation.

scholarly journals Contractile acto-myosin network on nuclear envelope remnants positions human chromosomes for mitosis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Alexander JR Booth ◽  
Zuojun Yue ◽  
John K Eykelenboom ◽  
Tom Stiff ◽  
GW Gant Luxton ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Mitotic Spindle ◽  
Dependent Manner ◽  
Linc Complex ◽  
Nuclear Envelope Breakdown ◽  
Cytoplasmic Surface ◽  
Chromosome Congression ◽  
Spindle Microtubules ◽  
Scattering Volume ◽  
Early Mitosis

To ensure proper segregation during mitosis, chromosomes must be efficiently captured by spindle microtubules and subsequently aligned on the mitotic spindle. The efficacy of chromosome interaction with the spindle can be influenced by how widely chromosomes are scattered in space. Here, we quantify chromosome-scattering volume (CSV) and find that it is reduced soon after nuclear envelope breakdown (NEBD) in human cells. The CSV reduction occurs primarily independently of microtubules and is therefore not an outcome of interactions between chromosomes and the spindle. We find that, prior to NEBD, an acto-myosin network is assembled in a LINC complex-dependent manner on the cytoplasmic surface of the nuclear envelope. This acto-myosin network remains on nuclear envelope remnants soon after NEBD, and its myosin-II-mediated contraction reduces CSV and facilitates timely chromosome congression and correct segregation. Thus, we find a novel mechanism that positions chromosomes in early mitosis to ensure efficient and correct chromosome–spindle interactions.

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