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Kinetochore-independent chromosome segregation driven by lateral microtubule bundles.

Muscat CC, Torre-Santiago KM, Tran MV, Powers JA, Wignall SM - Elife (2015)

Bottom Line: In this study, we show that lateral microtubule-chromosome associations established during prometaphase remain intact during anaphase to facilitate separation, defining a novel form of kinetochore-independent segregation.Chromosome dynamics during congression and segregation are controlled by opposing forces; plus-end directed forces are mediated by a protein complex that forms a ring around the chromosome center and dynein on chromosome arms provides a minus-end force.At anaphase onset, ring removal shifts the balance between these forces, triggering poleward movement along lateral microtubule bundles.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, United States.

ABSTRACT
During cell division, chromosomes attach to spindle microtubules at sites called kinetochores, and force generated at the kinetochore-microtubule interface is the main driver of chromosome movement. Surprisingly, kinetochores are not required for chromosome segregation on acentrosomal spindles in Caenorhabditis elegans oocytes, but the mechanism driving chromosomes apart in their absence is not understood. In this study, we show that lateral microtubule-chromosome associations established during prometaphase remain intact during anaphase to facilitate separation, defining a novel form of kinetochore-independent segregation. Chromosome dynamics during congression and segregation are controlled by opposing forces; plus-end directed forces are mediated by a protein complex that forms a ring around the chromosome center and dynein on chromosome arms provides a minus-end force. At anaphase onset, ring removal shifts the balance between these forces, triggering poleward movement along lateral microtubule bundles. This represents an elegant strategy for controlling chromosomal movements during cell division distinct from the canonical kinetochore-driven mechanism.

No MeSH data available.


Related in: MedlinePlus

Univalents lacking rings exhibit congression and segregation errors.(A) Oocytes from him-8(me4) and zim-2(tm574) worms stained for DNA (blue), AIR-2 or BUB-1 (red), and MPM-2 (green); each of these strains has two univalents (‘asterisks’). Rings are not detected on univalents, but kinetochore staining is present (BUB-1; bottom two rows). (B) Metaphase-arrested him-8(me4) bipolar and monopolar spindles, stained for DNA (blue), AIR-2 (red), and tubulin (green). During congression, univalents are randomly positioned on the bipolar spindle (top two rows), but were located near the pole on every monopolar spindle we observed (bottom). For quantification of bipolar spindles, univalents were scored as being at the center of the metaphase plate (zone 1), partially overlapping with the bivalents (zone 2), or not overlapping (zone 3). Examples of each category are indicated on the images. (C) him-8(me4) anaphase spindles stained for DNA (blue), MPM-2 (red), and tubulin (green). During segregation, univalents are either found near other segregating chromosomes (bottom) or lag behind in the center (top). Bars = 2.5 μm.DOI:http://dx.doi.org/10.7554/eLife.06462.018
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fig6: Univalents lacking rings exhibit congression and segregation errors.(A) Oocytes from him-8(me4) and zim-2(tm574) worms stained for DNA (blue), AIR-2 or BUB-1 (red), and MPM-2 (green); each of these strains has two univalents (‘asterisks’). Rings are not detected on univalents, but kinetochore staining is present (BUB-1; bottom two rows). (B) Metaphase-arrested him-8(me4) bipolar and monopolar spindles, stained for DNA (blue), AIR-2 (red), and tubulin (green). During congression, univalents are randomly positioned on the bipolar spindle (top two rows), but were located near the pole on every monopolar spindle we observed (bottom). For quantification of bipolar spindles, univalents were scored as being at the center of the metaphase plate (zone 1), partially overlapping with the bivalents (zone 2), or not overlapping (zone 3). Examples of each category are indicated on the images. (C) him-8(me4) anaphase spindles stained for DNA (blue), MPM-2 (red), and tubulin (green). During segregation, univalents are either found near other segregating chromosomes (bottom) or lag behind in the center (top). Bars = 2.5 μm.DOI:http://dx.doi.org/10.7554/eLife.06462.018

Mentions: Integrating our findings, our data support the model that there are opposing forces acting on oocyte chromosomes during congression and segregation, with plus-end directed forces originating in the rings countered by accumulating minus-end forces. To further test this idea, we assessed the behavior of chromosomes lacking rings by analyzing mutants where particular sets of homologous chromosomes are unable to pair (him-8(me4) and zim-2(tm574), where the X chromosome (Phillips et al., 2005) and chromosome V (Phillips and Dernburg, 2006) are affected, respectively), resulting in five bivalents and two unpaired chromosomes (univalents). These univalents were not recognized by antibodies against MPM-2 or the CPC component AIR-2/Aurora B, indicating that they do not form ring structures (Figure 6A, asterisks), and consequently each spindle had only five rings. However, the univalents were able to load kinetochore components, as BUB-1, which localizes to both the kinetochore and the ring (Monen et al., 2005; Dumont et al., 2010), coated their outer surfaces (Figure 6A).10.7554/eLife.06462.018Figure 6.Univalents lacking rings exhibit congression and segregation errors.


Kinetochore-independent chromosome segregation driven by lateral microtubule bundles.

Muscat CC, Torre-Santiago KM, Tran MV, Powers JA, Wignall SM - Elife (2015)

Univalents lacking rings exhibit congression and segregation errors.(A) Oocytes from him-8(me4) and zim-2(tm574) worms stained for DNA (blue), AIR-2 or BUB-1 (red), and MPM-2 (green); each of these strains has two univalents (‘asterisks’). Rings are not detected on univalents, but kinetochore staining is present (BUB-1; bottom two rows). (B) Metaphase-arrested him-8(me4) bipolar and monopolar spindles, stained for DNA (blue), AIR-2 (red), and tubulin (green). During congression, univalents are randomly positioned on the bipolar spindle (top two rows), but were located near the pole on every monopolar spindle we observed (bottom). For quantification of bipolar spindles, univalents were scored as being at the center of the metaphase plate (zone 1), partially overlapping with the bivalents (zone 2), or not overlapping (zone 3). Examples of each category are indicated on the images. (C) him-8(me4) anaphase spindles stained for DNA (blue), MPM-2 (red), and tubulin (green). During segregation, univalents are either found near other segregating chromosomes (bottom) or lag behind in the center (top). Bars = 2.5 μm.DOI:http://dx.doi.org/10.7554/eLife.06462.018
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fig6: Univalents lacking rings exhibit congression and segregation errors.(A) Oocytes from him-8(me4) and zim-2(tm574) worms stained for DNA (blue), AIR-2 or BUB-1 (red), and MPM-2 (green); each of these strains has two univalents (‘asterisks’). Rings are not detected on univalents, but kinetochore staining is present (BUB-1; bottom two rows). (B) Metaphase-arrested him-8(me4) bipolar and monopolar spindles, stained for DNA (blue), AIR-2 (red), and tubulin (green). During congression, univalents are randomly positioned on the bipolar spindle (top two rows), but were located near the pole on every monopolar spindle we observed (bottom). For quantification of bipolar spindles, univalents were scored as being at the center of the metaphase plate (zone 1), partially overlapping with the bivalents (zone 2), or not overlapping (zone 3). Examples of each category are indicated on the images. (C) him-8(me4) anaphase spindles stained for DNA (blue), MPM-2 (red), and tubulin (green). During segregation, univalents are either found near other segregating chromosomes (bottom) or lag behind in the center (top). Bars = 2.5 μm.DOI:http://dx.doi.org/10.7554/eLife.06462.018
Mentions: Integrating our findings, our data support the model that there are opposing forces acting on oocyte chromosomes during congression and segregation, with plus-end directed forces originating in the rings countered by accumulating minus-end forces. To further test this idea, we assessed the behavior of chromosomes lacking rings by analyzing mutants where particular sets of homologous chromosomes are unable to pair (him-8(me4) and zim-2(tm574), where the X chromosome (Phillips et al., 2005) and chromosome V (Phillips and Dernburg, 2006) are affected, respectively), resulting in five bivalents and two unpaired chromosomes (univalents). These univalents were not recognized by antibodies against MPM-2 or the CPC component AIR-2/Aurora B, indicating that they do not form ring structures (Figure 6A, asterisks), and consequently each spindle had only five rings. However, the univalents were able to load kinetochore components, as BUB-1, which localizes to both the kinetochore and the ring (Monen et al., 2005; Dumont et al., 2010), coated their outer surfaces (Figure 6A).10.7554/eLife.06462.018Figure 6.Univalents lacking rings exhibit congression and segregation errors.

Bottom Line: In this study, we show that lateral microtubule-chromosome associations established during prometaphase remain intact during anaphase to facilitate separation, defining a novel form of kinetochore-independent segregation.Chromosome dynamics during congression and segregation are controlled by opposing forces; plus-end directed forces are mediated by a protein complex that forms a ring around the chromosome center and dynein on chromosome arms provides a minus-end force.At anaphase onset, ring removal shifts the balance between these forces, triggering poleward movement along lateral microtubule bundles.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, United States.

ABSTRACT
During cell division, chromosomes attach to spindle microtubules at sites called kinetochores, and force generated at the kinetochore-microtubule interface is the main driver of chromosome movement. Surprisingly, kinetochores are not required for chromosome segregation on acentrosomal spindles in Caenorhabditis elegans oocytes, but the mechanism driving chromosomes apart in their absence is not understood. In this study, we show that lateral microtubule-chromosome associations established during prometaphase remain intact during anaphase to facilitate separation, defining a novel form of kinetochore-independent segregation. Chromosome dynamics during congression and segregation are controlled by opposing forces; plus-end directed forces are mediated by a protein complex that forms a ring around the chromosome center and dynein on chromosome arms provides a minus-end force. At anaphase onset, ring removal shifts the balance between these forces, triggering poleward movement along lateral microtubule bundles. This represents an elegant strategy for controlling chromosomal movements during cell division distinct from the canonical kinetochore-driven mechanism.

No MeSH data available.


Related in: MedlinePlus