New Insights into the Role of BubR1 in Mitosis and Beyond - International Review of Cell and Molecular Biology - page 223

depolymerization of the MTs. This in turn generates an unattached kinet-
ochore which is then free to form proper attachments ( Lampson and
Cheeseman, 2011 ). Several studies support the notion that Aurora
B activity can specifically destabilize abnormal K-MT attachments, such
as syntelic or merotelic chromosomes ( Ditchfield et al., 2003; Hauf et al.,
2003; Kallio et al., 2002; Murata-Hori and Wang, 2002 ). Among the kinet-
ochore proteins whose phosphorylation by Aurora B promote the detach-
ment of MTs are Hec1, a subunit of the Ndc80 complex ( Cheeseman et al.,
2006; DeLuca et al., 2006 ), and MCAK (mitotic centromere-associated
kinesin), a kinesin whose function is to depolymerize incorrectly attached
microtubules ( Andrews et al., 2004; Kline-Smith et al., 2004; Knowlton
et al., 2006; Lan et al., 2004 ).
2.3. Kinetochore assembly
Not only are kinetochores the sites of attachment of spindle microtubules,
they also are the platform on which the SAC apparatus is assembled. Kinet-
ochores thus play a central role in assuring faithful chromosome segregation.
We briefly introduce here only the outer kinetochore components believed
to interact with BubR1. When a vertebrate cell enters mitosis, the compo-
nents of kinetochores are assembled at the centromeres of each chromatid,
on the preexisting protein platform comprised of the constitutive
centromere-associated network (CCAN), which as its name suggests is
present throughout the cell cycle. A set of proteins called the KMN network
(comprised of the KNL1, Mis12, and Ndc80 protein subcomplexes) forms
the evolutionarily conserved core of the mitotic kinetochore structure
involved in MT binding and SAC function ( Varma and Salmon, 2012 ).
Mis12 and Ndc80 are themselves assemblies of several proteins. The
Ndc80 complex, for example, contains four proteins (Ndc80, Nuf2,
Spc24, and Spc25), which together form the principle anchor for mature
K-MT attachments, although KNL1 also has a microtubule binding activity
( Cheeseman et al., 2006; DeLuca et al., 2006; Espeut et al., 2012; Wei et al.,
2007; Welburn et al., 2010 ).
The KMN network in turn recruits other important microtubule motors
and regulators. These include components of the SAC apparatus (Bub1,
BubR1, Mps1, Mad1, Mad2) and associated proteins such as the RZZ com-
plex, and proteins such as cytoplasmic Dynein, Spindly, Clasps, CenpE, and
the Ska complex, which play important roles in establishing the proper
attachment and biorientation of chromosomes on the mitotic spindle. Once