New Insights into the Role of BubR1 in Mitosis and Beyond - International Review of Cell and Molecular Biology - page 247

chromosome segregation in meiosis, see reviews by Clift and Marston
(2011) , Fraune et al. (2012) , Petronczki et al. (2003) , and Takeo and
Hawley (2012) . Thus, while meiosis is mechanistically related to mitosis,
it involves a number of unique steps that may require variations of, and addi-
tions to, the known mitotic control mechanisms. The question concerning
us here is twofold: (1) Does BubR1 play a role in the SAC and in promoting
K-MT attachment in meiosis as it does in mitosis? (2) Does BubR1 play any
additional roles in meiosis?

5.1.1 functions of BubR1 in meiosis

Initially, there was doubt whether the SAC was even functional in mamma-
lian meiosis, at least in meiosis I. Meiotic divisions are highly error-prone in
humans ( Hassold and Hunt, 2001; Nagaoka et al., 2012 ), and the incidence
of missegregation in oocytes rises rapidly with the age of the mother. More-
over, in meiosis I, sister kinetochores of each homologue must attach to the
same pole of the spindle (monopolar orientation), a situation that in mitosis
would be detected as an attachment error. But different studies using mouse
knock-out models, protein overexpression, dominant negative mutants, and
knockdown approaches have convincingly shown that the SAC is very
much functional in mammalian female meiosis I ( Brunet et al., 2003;
Hached et al., 2011; Homer et al., 2005; Li et al., 2009; McGuinness
et al., 2009; Wassmann et al., 2003; Wei et al., 2010; Yin et al., 2006 ).
The meiosis I SAC delays the metaphase-anaphase transition if kinetochores
are not attached, but does not recognize the (normal) monopolar attachment
of bivalent sister kinetochores as incorrect. Genetic elimination of the
checkpoint components Mad2, Bub1, and Mps1 in the mouse all increase
chromosome missegregation in meiosis I and shorten the duration of
prometaphase ( Hached et al., 2011; McGuinness et al., 2009; Niault
et al., 2007 ). As one might expect, complete loss of SAC control causes ste-
rility. Still, it seems that the SAC is not very efficient in oocyte meiosis since
the presence of one or two univalents does not prevent metaphase-
to-anaphase transition. Moreover, a single unpaired chromosome may
sometimes attach to the spindle in a bipolar manner (as in mitosis), and it
seems that the SAC is not able to recognize this as incorrect in meiosis
I( Nagaoka et al., 2012 ). This “meiotically challenged” SAC may contribute
to the high error rate observed in mammalian oocytes ( Nagaoka et al., 2012 ).
The role of BubR1 in the meiotic SAC is less clear than for the other
SAC components. Baker et al. (2004) reported that mouse oocytes with just
10% of normal BubR1 levels progressed from meiosis I to meiosis II with

“ Classical ”