New Insights into the Role of BubR1 in Mitosis and Beyond - International Review of Cell and Molecular Biology - page 224

assembled during prophase, the KMN network is present throughout mito-
sis, whereas many of the SAC and motor components are only abundant on
unattached kinetochores ( Dorn and Maddox, 2012; Hoffman et al., 2001;
Howell et al., 2001, 2004 ). As the KMN network is the platform for both
microtubule binding and the SAC components, it provides a key link coor-
dinating K-MT attachment and the spindle checkpoint response. The
KNL1 subunit of the KMN network appears to be the major binding pro-
tein recruiting both Bub1 and BubR1 to kinetochores ( Bolanos-Garcia
et al., 2011; D'Arcy et al., 2010; Kiyomitsu et al., 2007; Krenn et al., 2012 ).
3. BubR1 STRUCTURE
The general domain architecture of vertebrate BubR1 is shown in
Fig. 6.1 . Human BubR1 is 1050 residues long. On both structural and func-
tional grounds, we can divide the protein into three regions: the N-terminal
region (residues 1-426), covering most of the sequences conserved with
yeast Mad3, the C-terminal region (residues 730-1050) covering the kinase
domain, and the middle region between them. The N-terminal region is
the most highly conserved across eukaryotes and is involved in kinetochore
binding and checkpoint signaling. The middle and C-terminal regions are
involved in promoting stable K-MT attachments.
Figure 6.1 Schematic of BubR1 and Mad3 structure. The different domains are
described in the text.