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severely misaligned chromosomes. Moreover, they found that oocytes of
older, wild-type mice have severely reduced BubR1 protein levels,
suggesting that the increase in missegregation events observed in oocytes
from mothers of advanced age may in part be due to loss of BubR1. Other
studies ( Homer et al., 2009; Wei et al., 2010 ) used morpholino treatment
and siRNA, respectively, to deplete BubR1, and similarly reported that
bivalent chromosome alignment was compromised and that cold-stable
microtubules were severely reduced in these oocytes, suggesting that
BubR1 is promoting chromosome K-MT attachment, just as it does in
mitosis. However, whereas several studies ( Baker et al., 2004; Tsurumi
et al., 2004; Wei et al., 2010 ) found that BubR1-depleted oocytes (or
expressing a dominant negative BubR1 mutant) progressed through
prometaphase I in an accelerated manner and entered anaphase much earlier
than control oocytes, Homer et al. (2009) reported that oocytes depleted of
BubR1 could not progress beyond metaphase I. These different phenotypes
might be caused by different degrees of BubR1 depletion, if one assumes
that SAC arrest and promotion of K-MT interactions all have different min-
imum BubR1 requirements. For example, the depleted oocytes in Homer
et al. (2009) may not have enough BubR1 to efficiently promote K-MT
attachment, but the level may be adequate for the ensuing SAC arrest. Over-
all, however, these results argue that the major mitotic functions of BubR1
in the SAC and in promoting K-MT attachment are also needed during
mammalian female meiosis.
5.1.2 Additional meiotic functions
5.1.2.1 Synaptonemal complex and sister chromatid cohesion
There are some indications that BubR1 may have additional, though less
well characterized, roles in meiosis. In early meiotic prophase, a structure
called the synaptonemal complex (SC) forms during the pairing (synapsis)
of homologous chromosomes. The SC is necessary to maintain homologue
pairing and for initiation of homologous recombination. In later prophase
(the diplotene stage), most of the SC is disassembled, but some persists in
the centromere region. Centromeric SC plays an important role first for
the initiation of synapsis and later for correct segregation of chromosomes
in anaphase I, at least in yeast and flies ( Gladstone et al., 2009; Newnham
et al., 2010; Takeo et al., 2011 ).
In Drosophila , males and females homozygous for BubR1 D1326N , a viable,
hypomorphic allele with an apparently normal mitotic SAC activity, were
found to generate frequent meiotic segregation errors, associated with a
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