Biology Reference
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Fig. 17.4 Spindle tension is required for centrosomal clustering. Model of centrosomal
clustering (left spindle half) and mechanisms involved in its prevention via reduction of spindle
tension (right spindle half). Centrosome clustering is brought about by microtubule tension-
dependent uniform positioning of individual centrosomes resulting in the formation of two
spindle poles. Spindle tension can be disrupted by reduction of chromatid cohesion (1) (Uzbekov
and Prigent
2007
), disturbed microtubule-kinetochore attachment (2) (Gould and Borisy
1977
),
reduced microtubule generation (3) (Doxsey et al.
1994
), disturbed microtubule bundling (4)
(Stearns et al.
1991
), or interference with the interphase cell adhesion pattern by disruption of
components of the actin cytoskeleton (5) (Bornens
2002
)
exert less tension and are destabilized, providing chromosomes a new opportunity to
bi-orient (Liu et al.
2009
). The mitotic kinase aurora B, the enzymatically active
component of the chromosomal passenger complex (CPC), localizes to the inner
centromere between sister kinetochores, and regulates chromosome-spindle
attachments by phosphorylating kinetochore substrates, including the NDC80 MT-
binding complex (Liu et al.
2009
; Ruchaud et al.
2007
; Wei et al.
2007
). The CPC
composed of aurora B and its regulatory subunits INCENP, survivin, and borealin are
a key regulator of chromosome segregation and cytokinesis. Since tension across
centromeres widens spatial partition of the CPC and thereby separates aurora B from
its kinetochore substrates, substrate phosphorylation is reduced resulting in stabi-
lized MT-kinetochore interactions (Liu et al.
2009
).
Using genome-wide RNAi screening in human cancer cells with extra centro-
somes both NDC80 complex and CPC components were found to be involved in
centrosomal clustering (Leber et al.
2010
). In addition, shugoshin-like 1 (SGOL1), a
protein previously known to be involved in sensing spindle tension at budding yeast
kinetochores (Indjeian et al.
2005
), is necessary for centrosome clustering. Impor-
tantly, SGOL1 also contributes to the recruitment of the CPC to centromeres (Bo-
yarchuk et al.
2007
; Kawashima et al.
2007
; Vanoosthuyse et al.
2007
) while itself is
loaded onto histone H2A after histone phosphorylation by BUB1 in yeast and human
cells (Kawashima et al.
2010
; Yamagishi et al.
2010
). Fittingly, BUB1 knockdown
does cause centrosome declustering as well (Sluder et al.
1997
). Another recently
identified centromeric recruitment factor for the CPC is haspin (Wang et al.
2010
;
Kelly et al.
2010
). Haspin phosphorylates histone H3, thereby creating a docking site
for survivin in both Xenopus and human cells. Interestingly, depletion of haspin leads
to the generation of multiple spindle poles and disruption of mitotic spindle structure
