In both divisions, chromosomes are duplicated in the S phase of the cell cycle, resulting in forming a pair of the replicated chromosomes defined as sister chromatids Figure 1A. Figure 1. Chromosomes in mitosis and in meiosis. A Chromosomes in mitosis and in meiosis. During mitotic cell cycles left , homologous chromosomes behave independently. Sister chromatids are connected by mitotic cohesin Rad21 Scc1.
In meiosis I right , homologous chromosomes are paired and crossed via chiasmata. Rad21 locates in the arm region of chromosomes in both divisions, whereas meiotic cohesin Rec8 purple ring locates in both the arm and centromeric regions. Moa1 Meikin is a meiosis-specific kinetochore protein that protects centromeric Rec8 cohesin through the recruitment of shugoshin Sgo1 to centromeres and regulates attachment to microtubules through the recruitment of Polo kinase Plo1.
B Orientation of kinetochores. In mitosis left , sister kinetochores are bi-oriented in a back-to-back position. In meiosis I, sister kinetochores are oriented in a side-by-side position. Spindle microtubules, green. C—E Conversion of chromosome arrangement upon sexual differentiation in fission yeast. In interphase e. In reaction to mating pheromone D , telomeres get clustered to SPBs. Kinetochores are dissociated off SPBs. During meiotic prophase E , a cytoplasmic array of microtubules is tethered by Hrs1 at SPBs, thereby shaking the nucleus.
The SPB-led back-and-forth movement of the nucleus is called horse-tail nuclear movement. The molecular basis constituting meiosis-specific chromosome configuration is largely attributed to meiotic cohesin, in which kleisin subunit Rad21 is replaced by Rec8 Parisi et al. Rec8 is a cohesin expressed specifically during meiosis, and both cohesins are conserved in all eukaryotes from yeast to human [reviewed in Ishiguro ].
In meiosis, meiotic Rec8-cohesin, in addition to mitotic Radcohesin, decorates chromosomes to connect sister chromatids as well as homologous chromosomes which are linked by chiasmata. The difference of Rec8-cohesin and Radcohesin is their chromosomal localization. Rec8-cohesin can localize at the core centromeric region but Radcohesin cannot in both mitosis and meiosis.
Furthermore, Rec8-cohesin forms two distinct complexes, one with Psc3 for centromeric cohesion and the other with arm cohesion Kitajima et al.
The kinetochore is assembled at the centromere of a chromosome, which serves as a dock site for spindle microtubule emanated from the spindle pole Figure 1B. In mitosis, homologous chromosomes a pair of maternal and paternal chromosomes in diploid cells behave independently upon segregation, whereas in meiosis, homologous chromosomes are paired and a part of them are physically connected by chiasmata. In mitosis, sister kinetochores built on core centromeres of sister chromatids are oppositely oriented in a back-to-back manner bi-oriented; Figure 1B.
On the other hand, the orientation in meiosis is converted to mono-orientation, in which the sister kinetochores are united in a side-by-side manner Figure 1B. The mono-orientation is constructed by Rec8-cohesin and monopolin proteins Moa1 in fission yeast; Spo13 and Mam1 in budding yeast Lee et al. Moa1 is a meiosis-specific kinetochore protein and is later found to be a member of the Meikin family together with Spo13 in budding yeast Kim et al. Moa1 together with the Rec8-cohesin located at core centromeres ties up kinetochores of sister chromatids facing toward the same direction so that the sister kinetochores can be mono-oriented meiosis, Figure 1B ; Yokobayashi and Watanabe, ; Kim et al.
The mono-orientation of sister kinetochores is maintained until anaphase of meiosis I anaphase I to ensure reductional division but is resolved to the mitotic bi-oriented style by the onset of meiosis II equational division. In mutants lacking Rec8 or Moa1, sister kinetochores are split and bi-oriented, and the division pattern of meiosis I results in equational division, as is seen in wild-type mitosis and meiosis II.
Thus, mono-orientation of kinetochores mediated by Rec8 and Moa1 is essential for the establishment of reductional division in meiosis I Figure 1B. Thus, meiotic kinetochore protein Meikin constitutes the mono-orientation of sister kinetochores as well as protects meiotic cohesin at centromeres through the recruitment of shugoshin. Shugoshin recruits PP2A to counteract the phosphorylation of the kleisin subunit of the cohesin complex to prevent cleavage Kitajima et al.
These two functions of Meikin are conducted via Polo kinase. Polo kinase is one of the mitotic kinases which mainly localize to spindle poles [reviewed in Nigg and Zitouni et al. Plo1, the Schizosaccharomyces pombe Polo kinase, also localizes to SPBs during mitosis but localizes to meiotic kinetochores using Moa1 as a platform Figure 1A ; Kakui et al. Polo kinase at meiotic kinetochores with Moa1 thus dictates the mono-orientation of sister kinetochores via Rec8 or monopolin in budding yeast as well as the protection of centromeric cohesin via shugoshin.
In addition to those dual functions of Moa1—Plo1, we will later discuss additional roles regarding interaction with microtubules. A number of studies revealed that the geographical arrangement of chromosomes in the nucleus affects the behaviors of chromosomes essential to accomplish meiotic events. Most importantly, the location of the chromosomes in the nucleus directly affects the efficiency of meiotic recombination. A brief schematic overview of chromosome allocation in the nucleus of the fission yeast is summarized in Figures 1C—E.
In the interphase of mitotic cell cycles, the centromeres of all chromosomes are clustered near SPBs the centrosome equivalent in yeast species located at the nuclear periphery Rabl orientation, Figure 1C ; Funabiki et al. Zygotic meiosis occurs when a pair of haploid cells is fused through the mating process to form a diploid cell right before entry into meiosis.
In contrast, azygotic meiosis occurs when proliferating cells in a diploid state start meiosis without the mating process Cipak et al. Both in zygotic and azygotic meiosis the mating pheromones are secreted and received on the cell surface to induce differentiation via the MAP kinase cascade. The mating pheromone—MAPK pathway affects chromosome positioning at the initial stage of sexual differentiation.
First, as illustrated in Figure 1D , telomeres are clustered in reaction to the mating pheromone. Then, centromeres are dissociated from the SPBs after cell conjugation in the case of zygotic meiosis Chikashige et al. This means that the chromosome arrangement in the nucleus becomes upside-down from the original state Rabl orientation : telomeres are clustered at SPBs, whereas centromeres kinetochores are located far from SPBs Figure 1E. The bouquet configuration of chromosomes is highly conserved throughout eukaryotes, which is essential to promote meiotic recombination [reviewed in Scherthan ].
A cytoplasmic array of microtubules is assembled particularly during meiotic prophase, and the minus ends of such microtubules are tethered at the SPBs. A meiosis-specific coiled-coil protein, Hrs1 also known as Mcp6 , localizes to SPBs and anchors the cytoplasmic array of microtubules at their minus ends Figure 1E , which serves as a fulcrum at the SPBs that transmit the dynamic motion of microtubules to the oscillatory nuclear movement Saito et al.
The SPB-led microtubule array is dynamically reformed to pull and push the SPBs and the accompanying nucleus in the cytoplasm, by which the nucleus repeats a back-and-forth movement in the cytoplasm during meiotic prophase Chikashige et al.
The molecular mechanisms for clustering of telomeres have been intensively studied, and meiosis-specific telomere proteins Bqt1 and Bqt2 bouquet proteins play central roles for telomere clustering. Bqt1—Bqt2 binds to the constitutive telomere protein Rap1 and also associates nuclear membrane proteins Sad1—Kms1 and Kms2 Figure 1D ; Chikashige et al. The whole complex is called linker of nucleoskeleton and cytoskeleton LINC , and it brings all the telomeres toward SPBs by sliding along the nuclear envelope using the cytoplasmic microtubules tethered at SPBs.
Systems to rearrange chromosome positions in eukaryotes are generally conserved: cytoskeleton such as actin in the budding yeast Saccharomyces cerevisiae or microtubule in S. For instance, in mice germ cells, Majin serves as a related function in the linkage of telomeres and the nuclear envelope as a functional homolog of Bqt4, another transmembrane bouquet protein connecting telomeres and inner nuclear membrane Chikashige et al. Thus, SUN-KASH proteins are widely employed among eukaryotes to dynamically alter chromosome arrangement inside the nucleus during meiosis [reviewed in Chikashige et al.
In addition, the telomere bouquet may regulate spindle functions. The first report described that if the bouquet formation is defective e. This is mostly due to the SPB-led horse-tail nuclear movement: SPBs are often apart from the main nuclear body after frequent shaking by cytoplasmic microtubules because the spindle phenotype can be rescued by interrupting the nuclear movement Chikashige et al.
In mitosis and meiosis, the association of centromeres to SPBs promote mitotic spindle formation Fennell et al.
Taking this knowledge together, we can generalize that chromosome configuration controls the spindle. Another study reported that bouquet formation contributes to the correct attachment of kinetochores and microtubules in subsequent meiosis I.
The bouquet-deficient strains e. It is also reported that telomere bouquet is required to activate the cyclin-dependent kinase-cyclin B CDK-cyclin B at SPBs at the later stage of meiotic prophase Moiseeva et al. Bouquet-deficient cells also show defects in the detachment of centromeres from SPBs illustrated in Figure 1D , indicating that the detachment of centromeres and the collection of telomeres toward SPBs are linked to each other by the LINC complex and microtubules Katsumata et al.
Another essential phenomenon seen during the initial stage of meiotic events is reorganization of kinetochore and SPB components. In fission yeast, most of the kinetochore components, including both inner and outer factors, stably constitute kinetochores throughout the mitotic cell cycle.
There are only few exceptions: the Dam1 complex is a mitosis-specific kinetochore component, while the Mis18 complex disappears in mitosis Hayashi et al. Components of fission yeast tend to be constitutive in contrast to those of metazoans.
The modification of kinetochore proteins by mitotic kinases might have been developed during the evolution from yeast to metazoans. Signaling via the mating pheromone—MAPK pathway in the early stage of meiosis is responsible for the disappearance of the kinetochore components. A reason for making slim kinetochores is for the detachment of centromeres from SPBs Figure 1D , through which chromosomes get inverted to promote pairing and recombination.
In budding yeast meiosis, kinetochores detach from the SPB as in fission yeast meiosis. It is suggested that the dissociation of outer kinetochore components may trigger the recruitment of Mam1 monopolin to kinetochores for mono-orientation at meiosis I Meyer et al.
Plo1 localizes instead to kinetochores as mentioned above. It gets localized to SPBs later, upon entry into meiosis I. The slimming down of SPB components shares similarities with that of kinetochore components. Another advantage for dynamic SPB reorganization is to temporarily deposit Plo1 to kinetochores at meiosis I onset: reducing Plo1 at SPBs to get priority to depositing it at kinetochores.
The kinetochore localization of Plo1 plays crucial roles in the collection of dispersed kinetochores before meiosis I entry see below. The slimming down of SPBs is not evident in budding yeast meiosis, although only a small number of SPB-associated proteins fluctuate: for instance, a meiosis-specific S.
The discrepancy in yeast species might be due to SPB structures. A budding yeast SPB is a three-layered structure and is embedded to the nuclear envelope throughout the cell cycle, whereas a fission yeast SPB has an amorphous structure and is inserted into the nuclear envelope prior to M phase entry Ding et al.
It is possible that fission yeast SPB is structurally flexible compared to that of budding yeast and that the plasticity may allow a reorganization of the components. Thus, in mitosis, the components of kinetochores and SPBs are almost constitutive, whereas there are a number of reorganizations taking place probably to streamline cellular machineries to adapt for divisions specialized for the production of gametes.
Data remain elusive regarding molecular mechanisms as to how slimmed kinetochores and SPBs are rebuilt right before entry into meiosis I. Previous studies indicated the requirement of activities of cell cycle kinases. In budding yeast, the activity of the Aurora B kinase Ipl1 is required for the reappearance of Ndc80 to kinetochores before meiosis I Kim et al. It is possible that those kinases phosphorylate some key components that are required for further recruitment of other components to reconstitute SPBs and kinetochores before entry into meiosis I.
Next, we compare the chromosome arrangement in the nucleus upon entry into mitosis and into meiosis I. As discussed above, centromeres kinetochores are located close to SPBs in the interphase of the mitotic cell cycle Figure 1C. This allocation is suitable for easy connection between microtubules and kinetochores upon entry into mitosis, as microtubules are nucleated from two SPBs, where kinetochores have been clustered even during interphase Figure 2A.
Figure 2. Chromosome arrangement changes upon sexual differentiation. Chromosome positioning upon entry into mitosis. At the onset of mitosis A , kinetochores red are clustered at spindle pole bodies SPBs; blue , where microtubules green start to nucleate. D—G Chromosomes are re-arranged upon entry into meiosis I right after the horse-tail nuclear movement is ceased D. Microtubules are nucleated from SPBs, but kinetochores are scattered in the nucleus.
Kinetochores are mono-oriented by Moa1 Meikin, purple , which recruits Polo kinase Plo1. Telomeres are dissociated from SPBs. At the timing when kinetochore retrieval is completed F , SPBs start to separate to assemble the bipolar spindle G.
Note that homologous chromosomes are independently attached to microtubules in mitosis C , whereas they are paired in meiosis I G. The SPBs, duplicated in interphase, are separated from each other on the surface of the nucleus, as microtubules emanated from each of the SPBs start to overlap and interdigitate upon mitotic entry Figure 2B. Finally, those two SPBs are separated to opposite sides so that the bipolar spindle can be assembled by metaphase Figure 2C.
On the contrary, in cells entering meiosis I, positioning of chromosomes is completely upside-down as a result of centromere dissociation and telomere clustering.
In addition, chromosomes are duplicated as sister chromatids, and homologous chromosomes are paired with chiasmata as a result of meiotic recombination during the horse-tail nuclear movement, as illustrated in Figure 2D. The upside-down positioning of chromosomes could be a potential risk for the subsequent chromosome segregation in meiosis I because kinetochores are located distal from the microtubule nucleation site, unlike that in mitosis.
When cells enter meiosis I, the horse-tail nuclear movement ceases, and microtubules are nucleated from SPBs toward inside the nucleus as observed at mitotic entry. In contrast to mitotic entry, meiotic cells, at this stage, start to nucleate an extensive radial array of microtubules from SPBs Figure 2D ; Kakui et al.
The extended microtubules then capture kinetochores scattered in the nucleus and then shrink to retrieve the attached kinetochores toward SPBs Figure 2E.
The retrieval of kinetochores mostly relies on depolymerization of microtubules rather than sliding of kinetochores on microtubules. First, a kinetochore may attach to the lateral surface of a microtubule, and this can then be converted to end-on pulling when the plus end of the shrinking microtubule reaches the kinetochore.
End-on pulling motion in meiotic kinetochore retrieval relies on the Dam1 complex, which forms oligomeric rings around microtubules Westermann et al. In contrast, budding yeast kinetochores are mainly collected by sliding on the surface of microtubules in mitosis Tanaka et al.
Homologous kinetochores are retrieved as a pair by microtubules, and mathematical modeling indicated that the dynamic instability of microtubules is essential for efficient retrieval and that paired configuration of kinetochores accelerates the capture by pivoting microtubules Cojoc et al. When homologous kinetochores are captured and pulled by microtubules, the mode of attachment may be mostly monopolar, the state in which both kinetochores are pulled by microtubules emanated from the same spindle pole.
This may be resolved by Aurora B kinase, as budding yeast meiotic kinetochores retrieved in a monopolar manner are converted to bipolar attachment through phosphorylation by the Aurora B kinase Ipl1 Meyer et al. The kinetochore protein Dam1 is also shown to promote chromosome bi-orientation through phosphorylation by the Mps1 kinase Meyer et al. During retrieval of kinetochores by pivoting monopolar microtubules, formation of the bipolar spindle separation of two SPBs should be repressed, although the system that surveys the completion of the scattered kinetochores does not appear very strict, as occasionally bipolar spindle starts to assemble even before the completion of kinetochore retrieval Kakui et al.
As Ndj1, Mps3, and Csm4 are also involved in telomere positioning and motility in meiotic prophase, loss of Ndj1 in meiosis I brings two consequences: SPB separation and telomere dissociation from the nuclear envelope Conrad et al. In summary, the extensive microtubules are assembled to relocate chromosomes to the original position as seen in mitotic entry, thereby minimizing the potential risk of segregation errors in meiosis I.
In addition to the assembly of radial microtubules, cells at meiosis I onset take the second strategy, namely, cells utilize Alp7 also known as Mia1 , the S. Alp7 primarily localizes to SPBs and microtubules. Alp7 also localizes to mitotic kinetochores once captured by spindle microtubules, which means that Alp7 is delivered to kinetochores by microtubules and stabilizes kinetochore—microtubule attachment in mitosis Oliferenko and Balasubramanian, ; Sato et al.
Although Alp7 localizes also to meiotic kinetochores, it is of note that Alp7 localizes there even before microtubule attachment Figure 2D.
Alp7 precociously localized to scattered kinetochores promotes capture by radial microtubules Kakui et al. Thus, cells employ two machineries—extension of radial microtubules and precious localization of Alp7 to kinetochores— to synergistically promote relocation of chromosomes.
Do these machineries operate also during mitosis or only during meiosis? The radial array of microtubules is not evident in cells at mitotic onset, in which kinetochores are constantly located in the vicinity of SPBs.
When kinetochores are artificially detached from SPBs upon entry into mitosis, for example, by the use of transient exposure to microtubule poisons, similar long microtubules are assembled after drug washout to capture and collect the scattered kinetochores.
Thus, the machinery utilizing extending microtubules may also operate during mitosis as a backup system to respond to the unexpected risk, although it has not been clarified if the molecular mechanisms for microtubule extension are identical in mitosis and in meiosis.
Alternatively, either SPB separation or maturation in meiosis I could be repressed by slim SPBs during meiotic prophase to efficiently form a radial microtubule array.
In meiosis, however, extension of microtubules is observed in cells at the stage without exception, and the microtubules complete kinetochore retrieval mostly by the time SPBs start to separate Figures 2F,G , suggesting that the scheme in meiosis is programmed as a physiological system rather than as a reflex action to the contingency. The second strategy, namely, the precocious deposition of Alp7 to microtubule-free kinetochores, is exclusively observed in this stage, and a similar localization cannot be observed in mitotic cells.
Thus, deposition of Alp7 to pre-attached kinetochores is programmed specifically for meiosis. This is indeed evidenced by the molecular mechanism underlying the precocious localization of Alp7 to meiotic kinetochores: the meiosis-specific localization of Alp7 is dependent on the Polo kinase Plo1, which is also located to pre-attached kinetochores in meiosis Figure 2D. As mentioned above, Plo1 localizes to pre-attached kinetochores using Moa1 Meikin as a platform; therefore, Alp7 localization to the kinetochores is also a meiosis-specific event.
Taken together, we consider that Moa1—Plo1 plays the third function in meiosis—at the onset of meiosis I, kinetochores are highlighted as center for microtubule control: Moa1 Meikin recruits Plo1 Polo kinase , which deposits Alp7 TACC to stably capture microtubules emanated radially from spindle poles.
Moa1—Plo1 has an additional role: Plo1 at meiotic kinetochores also phosphorylates Spc7 KNL1 of the outer kinetochore components. This affects the localization of Bub1 kinase which is known as a checkpoint kinase and phosphorylates histone H2A to recruit shugoshin at centromeres Tang et al.
In mitosis, the kinetochore localization of Bub1 is transient, whereas Bub1 in meiosis persists at kinetochores until anaphase of meiosis I because Spc7, the platform for Bub1, is phosphorylated by Plo1 specifically in meiosis Miyazaki et al.
Thus, Moa1—Plo1 plays a central role to dictate a number of meiosis-specific events regarding the interaction of kinetochores and microtubules, thereby differentiating meiosis from mitosis. The progression of kinetochore—microtubule association is monitored by the spindle assembly checkpoint SAC machinery in mitosis and meiosis.
Briefly, kinetochores unattached to microtubules are recognized by the Mad1—Mad2 complex, the main components of SAC. When chromosomes are repositioned at the onset of meiosis I, the unattached kinetochores are not recognized by Mad1—Mad2. This is probably due to a lack of sufficient CDK activity, which is a prerequisite for the localization of Mad1—Mad2 to unattached kinetochores Aoi et al.
For an entire resolution of the bouquet arrangement, telomeres that have been clustered around SPBs during meiotic prophase are detached from SPBs upon entry Figure 2E , although the molecular mechanism remains elusive. Resolution of telomere clustering occurs almost at the same timing with kinetochore retrieval, albeit slightly later than the retrieval. The resolution requires elevation of the cyclin-dependent kinase activity by Cdc25 phosphatase, which is transcriptionally activated by the meiosis-specific transcription factor Mei4 Murakami-Tonami et al.
Cdc13 cyclin B predominantly accumulates at bouquet telomeres for the resolution of telomere clustering Moiseeva et al. It has been recently shown that difference in chromosome configuration in mitosis and meiosis affects bipolar spindle organization using their kinetic properties. The assembly of bipolar spindle is based on the elongation of microtubules and their mutual and physical interaction. Spindle microtubules are emanated from both of the two SPBs, and they interact with each other to separate the SPBs outward, which is the major driving force for bipolar spindle formation.
As illustrated in Figure 3A , a couple of kinesin motor proteins are involved in the separation of two SPBs. Kinesin-5 is a conserved subfamily of the kinesin superfamily motor proteins that move to plus-ends and functions as a homo-tetramer Hagan and Yanagida, , ; Kapoor et al.
Cut7, the fission yeast ortholog of kinesin-5 subfamily members, is an essential protein required for outward SPB separation that functions as a tetramer Hagan and Yanagida, , ; Akera et al. Cut7 captures the lateral surface of a pair of interpolar microtubules emanating from both SPBs, and it moves toward their plus-ends along the microtubules.
Figure 3. Force balance affects spindle pole body SPB separation in mitosis and meiosis. A tetramer of Cut7 red captures two bundles of microtubules. When they are aligned in an anti-parallel manner, the plus-end-directed Cut7 generates the outward force that consequently separates two SPBs.
Microtubules are tethered to SPBs at their minus ends. Pkl1 localizes to SPBs and Klp2 to the microtubules. Those minus-end-directed motors generate the inward force. B SPB separation in prometaphase of mitosis. D When Swi6 HP1 is deleted, the structure of sister kinetochores is loosened, which does not generate a sufficient repulsive force to separate SPBs.
On the contrary, members belonging to another subfamily kinesin Pkl1 and Klp2 are minus-end-directed and generate inward forces for SPBs Figure 3A. Pkl1 preferentially localizes to SPBs and the spindle as well as the nucleoplasm during mitosis, and Klp2 localizes to spindle microtubules Pidoux et al.
In the absence of two antagonistic kinesins Cut7 and Pkl1, the outward force wins again to consequently separate the SPBs mitosis, Figure 3C. This also indicates that there are additional factors that generate the outward force to separate SPBs other than Cut7.
One of such factors is the microtubule-associated protein Ase1 human PRC1 , which is known to connect a pair of interdigitating microtubules as an anti-parallel bundle Pellman et al. Similarly, other microtubule-associated proteins promote outward force generation in the absence of Cut7 Yukawa et al. In addition to microtubule-associated proteins, chromosome is another factor that generates outward force for SPB separation. The microtubules use the sister kinetochores as the fulcrum to generate the repulsive force which separates SPBs.
This is evidenced by genetic analyses; for instance, SPB separation is inhibited when the mitotic cohesin Rad21 is removed i. Moreover, when the sister kinetochores are unfastened by reduction of centromeric cohesion using deletion of Swi6 HP1 Ekwall et al. These results altogether demonstrate that centromeric cohesion and functional sister kinetochores are required for generation of the outward force in the absence of Cut7 and Pkl1.
This is due to the loosened connection between homologous kinetochores instead of a tight sister kinetochore connection of mitotic cells Figure 3E. When mono-orientation of sister chromatids is converted to bi-orientation by deletion of Moa1 i.
This provides us two concepts. First, the rigidity of the kinetochore connection matters because it determines whether an additional outward force for SPB separation is generated in mitosis and in meiosis. Second, the kinetochore-mediated outward force is weaker in meiosis I than in mitosis, owing to meiotic kinetochore mono-orientation.
This may lead to a delay in SPB separation in meiosis I, unless the Cut7-mediated force is somehow augmented or the opposing inward force by kinesin motors decreases. When kinetochores are retrieved to the close vicinity of SPBs, it may be able to generate a rigid repulsive force by short microtubules that is sufficient for SPB separation. This may be reasonable for cells at this stage, as they need to earn some additional time until all the scattered kinetochores are collected to SPBs.
Thus, the kinetochore-mediated repulsive force may modulate the balance of mechanical forces, through which meiosis-specific cell cycle progression and chromosomal events may be timely coordinated. In general, either in mitosis or meiosis, fission yeast microtubules do not complete end-on attachment to kinetochores by the timing of SPB separation. Therefore, the kinetochore-mediated SPB separation may not rely on the end-on attachment; rather, a pair of bi-oriented kinetochores serves as a glue factor that connects two anti-parallel microtubules through attachment to their lateral surfaces, similarly to the microtubule-associated bundling factor Ase1.
Kinetochore-driven centrosome separation has also been observed in HeLa cells. When a kinetochore protein, either CENP-O Mcm21 or CENP-L, is depleted, separation of centrosomes is delayed albeit partially, and this is due to defects in the formation of kinetochore microtubules kinetochore fibers or k-fibers Toso et al. There are two major pathways for centrosome separation in HeLa mitosis: the aurora A-dependent pathway, which is presumably for centrosomal microtubule-mediated separation, and the kinetochore-dependent pathway Toso et al.
When the nuclear envelope breakdown precedes centrosome separation in prometaphase, lateral attachment and kinetochores to microtubules and their lateral transport are promoted to form a ring-like alignment of chromosomes, called prometaphase rosette Nagele et al. The prometaphase rosette is gradually converted to metaphase congression through the transport of laterally attached kinetochores by the kinesin-7 motor CENP-E and the chromokinesin Kid Tokai et al.
Kinetochore-driven centrosome separation may occur during the conversion and establishment of the metaphase alignment. These observations imply that the way of kinetochore-mediated SPB separation is an analogous phenomenon to the similar centrosome separation. During acentrosomal meiosis I of mouse oocytes, the Ndc80 complex of outer kinetochores accumulate the microtubule crosslinker Prc1 yeast Ase1 to kinetochores, which becomes a center for microtubule bundling to assemble the functional bipolar spindle even without positional cues at spindle poles Yoshida et al.
As mentioned above, the SAC machinery monitors the state of kinetochore—microtubule interaction, and in the case of problems, SAC arrests cell cycle progression in metaphase. SAC detects two types of erroneous interactions: an improper attachment and a lack of tension between kinetochores Nezi and Musacchio, The overall functions of SAC are common in mitosis and in meiosis, but tension is generated in a different manner.
In mitosis, tension by microtubules is generated between sister kinetochores left, Figure 1B , whereas it is generated between homologous kinetochores right. In anaphase I, homologous chromosomes with chiasmata are segregated; hence, chiasmata need to be resolved by anaphase onset. SCF constitutes a conserved ubiquitin ligase family and contributes a number of cellular phenomena, and the fission yeast orthologs of the components are Skp1, Cul1, and at least 18 F-box proteins [reviewed in Toda et al.
In the temperature-sensitive mutant of SCF—Skp1 skp1 -ts , the anaphase spindle becomes abnormally bent in the nucleus, both in mitotic and meiotic anaphase Lehmann and Toda, ; Okamoto et al. The bend spindle in anaphase I is due to unresolved meiotic recombination intermediates that remained until anaphase as evidenced by the prolonged foci of Rad51 the RecA homolog indicating sites of meiotic recombination Muris et al. When meiotic cohesin Rec8 or the meiotic endonuclease Spo11 the fission yeast ortholog is named Rec12 is deleted, the bent spindle phenotype is suppressed, verifying that entangled chromosomes by prolonged recombination intermediates attached to microtubules hamper the full elongation of the anaphase spindle; therefore, the spindle is bent.
In conclusion, Skp1 and the F-box helicase Fbh1 are required for the resolution of meiotic recombination intermediates, although it remains to be elucidated which protein is targeted by SCF-Skp1—Fbh1 for degradation for the resolution Okamoto et al. The function of SCF—Skp1 in the resolution process appears conserved in eukaryotes: the Arabidopsis ask1 mutant Ask1 is the Skp1 ortholog has the spindle which displays an overall normal structure but somewhat longer than that of WT cells during meiosis I Yang et al.
The difference in spindle morphology bent or long in these two organisms could be simply due to whether the spindle poles are embedded in the nuclear envelope and whether the spindle is assembled in the compartmentalized nucleus in closed mitosis Figure 4A , and the function in resolution of meiotic intermediates is likely to be conserved.
Figure 4. Meiosis-specific cell cycle progression from meiosis I to meiosis II. After anaphase I, only one of two nuclei is chosen for drawing to illustrate MII progression. At the transition stage of metaphase to anaphase, each SPB is modified, and the globular forespore membrane FSM begins to grow to surround the nucleus. The leading edge of the FSM opening is decorated by leading edge proteins. During anaphase II, the barrier function of the nuclear envelope is invalidated, which is an incident called virtual nuclear envelope breakdown.
After completion of MII, the rigid spore wall is assembled. B The kinetics of the CDK activity during meiosis. The horizontal axis time is shared with the time scale in A. The cells then start the aberrant third division albeit incomplete. One of the most enigmatic mechanisms of meiosis is two consecutive rounds of cell division: meiosis I MI and meiosis II MII without replicating DNAs, which is a clear contrast to the single M phase per cell cycle in mitotically growing cells.
Specialized regulation of CDK is essential for the interkinesis period, followed by the initiation of meiosis II. The drug-sensitive mutant cdc2-as analog-sensitive Dischinger et al. The cdc2-as mutant is deficient in meiosis II initiation and terminates meiosis in a binucleate state even without exposure to the ATP analog.
The activity of the mutant protein can be regained by the introduction of a suppressor mutation into the Cdc2-as protein. The cdc2-asM17 mutant has additional mutations to improve the Cdc2-as activity and proceeds meiosis normally to produce normal spores Aoi et al.
Really nice and clear to understand. Table makes it easy to tell the difference between the two, thank you so much. Save my name and email in this browser for the next time I comment. Following are the differences between Mitosis and Meiosis: S.
Yes, mixing of chromosomes can occur. Reduced by half. Sex cells only: female egg cells or male sperm cells. Do not disappear completely in telophase I.
Ends with cytokinesis. Meiosis Diploid parent cell Consists of interphase, prophase, metaphase, anaphase and telophase but twice! In metaphase II individual chromosomes pairs of chromatids line up along the equator. Related Content:. What is mitosis? What is meiosis? What is a cell? What is a stem cell? How helpful was this page? What's the main reason for your rating? Which of these best describes your occupation?
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