Commentary
4017
Modifying sister chromatid cohesion for meiosis
Yoshinori Watanabe
Institute of Molecular and Cellular Biosciences, and SORST, Japan Science and Technology Agency, University of Tokyo, Yayoi 1-1-1, Tokyo
113-0032, Japan
e-mail: [email protected]
Journal of Cell Science 117, 4017-4023 Published by The Company of Biologists 2004
doi:10.1242/jcs.01352
Summary
Meiosis produces haploid gametes from diploid cells in two
stages that in many ways resemble mitosis. However, the
regulatory mechanisms governing kinetochore orientation
and cohesion at the first meiotic division are different from
those at mitosis: sister kinetochores are pulled forwards
from the same spindle pole at metaphase, and centromeric
cohesion is protected throughout anaphase. Consequently,
homologous chromosomes, rather than sister chromatids,
segregate to the opposite sides of a cell. The residual
cohesion around centromeres plays an essential role at the
Introduction
In proliferating cells, the sister chromatids segregate to
opposite sides of the cell during mitosis, thereby transferring
copies of chromosomes into each of the two daughter cells.
This process is called equational chromosome segregation. For
it to occur properly, corresponding sister chromatids must
attach to microtubules emanating from opposite poles (bipolar
attachment). The cohesion at kinetochores counteracts the
pulling force of the microtubules and plays an essential role in
bipolar attachment, which is stabilized by the tension generated
across the kinetochores. Only when all kinetochores come
under tension is the spindle checkpoint inactivated. This
provokes activation of the anaphase-promoting complex
(APC), leading to the ubiquitin-dependent destruction of
securin, a guardian of the specific endopeptidase separase. In
turn, the released separase cleaves the cohesin complexes that
hold sister chromatids together, thereby allowing the sisters to
be segregated to opposite poles by the forces pulling on the
spindle (Figs 1, 2) (Nasmyth, 2002; Uhlmann, 2003).
Meiosis is a specialized cell cycle that reduces the
chromosome number by half to allow fertilization during
sexual reproduction to generate one normal nucleus. It consists
of two rounds of chromosome segregation following a single
round of DNA replication. At the first meiotic division (meiosis
I), homologous chromosomes, rather than sister chromatids,
are pulled to opposite poles. Only at the second meiotic
division (meiosis II) do sister chromatids segregate as they do
in mitosis (Fig. 1) (Lee and Orr-Weaver, 2001; Petronczki et
al., 2003). Thus, meiosis I has a unique form of chromosome
segregation, and understanding its molecular mechanism is a
major challenge. Three crucial events at chromosomes must
take place correctly for meiosis I to proceed. First, homologous
chromosomes (homologues) pair to recombine, forming
chiasmata in which one sister chromatid from one homologue
is covalently attached to a sister chromatid from the other
second meiotic division, when spindle microtubules from
opposite poles attach to sister chromatids. Recent studies
have identified novel meiosis-specific kinetochore proteins,
such as monopolin and shugoshin, and indicate that specific
modifications in sister chromatid cohesion lie at the heart
of the regulation of meiotic chromosome segregation.
Key words: Sister chromatid cohesion, Meiosis, Monopolar
attachment, Centromeric protection, Cohesin, Monopolin, Shugoshin
homologue. Second, sister kinetochores must attach to
microtubules from the same spindle pole (monopolar
attachment). Therefore, spindles create tension only when
homologues are pulled in opposite directions because regions
distal to chiasmata physically link them. Third, only arm
cohesion must be destroyed during anaphase I, whereas
centromeric cohesion must persist; this results in the separation
of homologues but not sister chromatids. The residual
centromeric cohesion is important during meiosis II for bipolar
attachment of sister kinetochores (Miyazaki and Orr-Weaver,
1994). Here, I discuss the specific modifications of sister
chromatid cohesion in meiosis that underpin these events and
the molecular mechanisms behind them.
Cohesin complexes in meiosis
During mitosis, sister chromatid cohesion is carried out by
cohesin complexes comprising two SMC (for ‘structural
maintenance of chromosomes’) -family proteins – Smc1 and
Smc3 – and two non-SMC subunits – Rad21/Scc1/Mcd1 and
Scc3 (Nasmyth, 2002). Smc1-Smc3 heterodimers are proposed
to interact through their long coiled-coil stretches and embrace
sister chromatids. Scc1 is thought to lock their ends,
presumably with the aid of Scc3 (Fig. 2) (Haering and
Nasmyth, 2003). The disassembly of the cohesin complex
triggers sister chromatid separation, following cleavage of
Rad21/Scc1 by separase (Fig. 2).
During meiosis, the Rad21/Scc1 subunit is mostly replaced
by a meiosis-specific version, Rec8. If Rec8 is depleted in
meiosis, recombination, synaptonemal complex formation,
monopolar attachment (at least in fission yeast) and persisting
centromeric cohesion all fail to occur (DeVeaux and Smith,
1994; Parisi et al., 1999; Klein et al., 1999; Watanabe and
Nurse, 1999). Remarkably, these meiosis-specific properties of
chromosomes are not restored in rec8∆ cells when Rad21/Scc1
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Journal of Cell Science 117 (18)
Meiosis
Mitosis
Rec8
Metaphase I
Rad21
Metaphase
Fig. 1. Chromosome segregation in mitosis and meiosis. Sister
chromatid cohesion during mitosis, carried out by Rad21/Scc1
complexes, is lost along the whole chromosome length at
anaphase. During meiosis, Rec8 substitutes for the Rad21/Scc1
subunit of the cohesin complex. Consequently, sister chromatid
cohesion is lost in a stepwise manner, first along chromosome
arms during meiosis I and second in the vicinity of
centromeres during meiosis II.
Anaphase I
processes involved in meiotic chromosome cohesion
must initiate at the latest during DNA replication.
Additional meiosis-specific cohesin subunits have
been found in various organisms (Table 1). Mammalian
SMC1β is reportedly expressed only in testis (Revenkova
Metaphase II
et al., 2001) and is probably a meiosis-specific version of
Anaphase
SMC1. The role of SMC1b and its specific requirements
in meiotic sister chromatid cohesion and recombination
have recently been determined (Revenkova et al., 2004).
Mammals also have at least three Scc3-like proteins,
Anaphase II
SA1-SA3, and SA3 is meiosis specific (Prieto et al.,
2001). Fission yeast have two: the ubiquitous Psc3 and
the meiosis-specific Rec11. Interestingly, meiotic Rec8
complexes along chromosome arms largely contain
Rec11, whereas those in the vicinity of centromeres have Psc3
is expressed ectopically (Toth et al., 2000; Yokobayashi et al.,
(Kitajima et al., 2003b). The interaction between Psc3 and
2003). Meiosis-specific cohesin thus appears not merely to be
heterochromatin protein Swi6 [a fission yeast homologue of
a link holding sister chromatids together but also to engage in
heterochromatin protein 1 (HP1), which forms pericentromeric
other aspects of chromosome behaviour. Studies in mammals
heterochromatin structures] could partly account for this. Two
have suggested that meiotic cohesin core proteins recruit
Scc3-like proteins thus define distinct organizations of meiotic
the recombination apparatus (Eijpe et al., 2003; Pelttari et
cohesins at centromeres and in the chromosome arm
al., 2001) and promote synapsis between homologous
regions of fission yeast. Mammalian SA3 disappears from
chromosomes together with associated synaptonemalchromosomes during anaphase I and is not detected at
complex-specific proteins (Eijpe et al., 2000). Cohesins
centromeres (Prieto et al., 2001), whereas centromeric Rec8 is
establish sister chromatid cohesion during DNA replication
preserved (Eijpe et al., 2003; Lee et al., 2003). SA3 might play
(Uhlmann and Nasmyth, 1998). If meiosis is initiated
a role similar to that of Rec11.
artificially after mitotic DNA replication by ectopically
During mitosis, enrichment of cohesin at centromeres is
activating the meiosis-inducing network, meiotic cohesin does
important because centromeric cohesion plays a central role in
not appear to function, even though Rec8 complexes associate
counteracting the pulling force of the spindle and thus in the
with chromatin (Watanabe et al., 2001). Therefore, the
proper alignment of chromosomes at metaphase (Bernard and
exchange of mitotic cohesins for meiotic cohesins must occur
Allshire, 2002). By contrast, to facilitate the resolution of sister
prior to DNA replication. Studies of budding yeast suggest that
chromatids, arm cohesion is mostly lost during prophase
recombination occurs only after the passage of the replication
(Losada et al., 2002). However, this system might not be
fork (Borde et al., 2000; Cha et al., 2000). Thus, the regulatory
appropriate for meiosis, because cohesion along
chromosome arms plays a crucial role promoting
recombination and holding homologues tightly together
to ensure disjunction at meiosis I. This may be why a
Separase
specific arm cohesin component is produced in meiosis.
Budding yeast are exceptional in lacking the centromeric
heterochromatin HP1-cohesin enrichment system and
therefore may have relatively stronger arm cohesion,
which potentially explains why this organism lacks a
Scc1
Rec11 homologue.
(Rad21) Scc3
Smc1
Smc3
Sister
chromatids
Metaphase
Anaphase
Fig. 2. The cohesin complex and its dissociation by separase.
A proposed model for the cohesin complex and its dissociation
by separase. In mitosis, the onset of anaphase is triggered by
the separase-dependent cleavage of Rad21/Scc1, a cohesin
subunit that might bind the two ends of Smc1-Smc3
heterodimer and thereby hold sister chromatids. During
meiosis, Rad21/Scc1 is largely replaced by Rec8 and Psc3 is
partly replaced by Rec11.
Sister chromatid cohesion for meiosis
Table 1. Cohesin subunits and shugoshin in various
organisms
S. cerevisiae
Cohesin
S. pombe
Scc1/Mcd1
Rad21
Rec8*
Rec8
Scc3
Psc3, Rec11
Smc1
Psm1
Smc3
Psm3
Shugoshin Sgo1
Sgo1, Sgo2
Drosophila
Human
DRAD21
DREC8
DSA-1, DSA-2
DSMC-1
DCAP
MEI-S332
hHR21
hREC8
SA1, SA2, SA3
SMC1α, SMC1β
SMC3
Sgo1†, Sgo2†
*The bold characters represent meiosis-specific proteins.
†Mammal shugoshin has not been analysed for expression.
Recombination and arm cohesion are required for
the disjunction of homologues at meiosis I
Meiotic recombination is catalysed by Spo11, which initiates
formation of double-strand breaks and the ensuing repair
reaction. The recombinational strand exchange contributes
to the generation of genomic diversity of gametes. More
importantly, perhaps, it generates chiasmata, which are
physical links between homologues that secure two
homologues being pulled from opposite poles at meiosis I
(Carpenter, 1994). If recombination is abolished (e.g. by the
spo11 mutation), homologues fail to align properly on the
spindle and so segregate randomly at meiosis I (Klein et al.,
1999).
In fission yeast, the selective inactivation of Rec11 or Psc3
at meiosis can distinguish cohesin functions at centromeres and
along the arm regions (Kitajima et al., 2003b). The inactivation
of Psc3 does not influence arm cohesion at all, but both
monopolar attachment and persistence of centromeric cohesion
(centromeric protection) are impaired at meiosis I. By contrast,
rec11∆ cells preserve centromeric cohesion while exhibiting a
precocious separation of chromosome arms. Consequently,
rec11∆ causes a high incidence of non-disjunction of
homologues at meiosis I, illuminating the importance of arm
cohesion for ensuring homologue segregation.
Monopolar attachment at meiosis I
Sister kinetochores attach to microtubules emanating from
opposite spindle poles during mitosis or meiosis II – proper
attachment being ensured by mechanisms that monitor the
tension generated at kinetochores. A recent study in budding
yeast has indicated that a circular unreplicated chromosome
carrying two kinetochores widely separated from each other
preferentially establishes bipolar attachment at mitosis (Dewar
et al., 2004). This elegant experiment stressed the importance
of tension sensing rather than the geometry of kinetochores
for establishing bipolar attachment. Since homologues are
connected by chiasmata at meiosis I, tension is also produced
when sisters are pulled to the same pole but homologues are
pulled in opposite directions. However, tension might not be
the primary determinant of sister kinetochore orientation at
meiosis I, because monopolar attachment occurs even in
the absence of interaction between homologues (e.g. in
recombination-minus meiosis) (Klein et al., 1999; Yamamoto
and Hiraoka, 2003), in which case tension can be produced
only by the bipolar attachment of sister kinetochores.
Thus, the geometry of sister kinetochores might be a major
determinant in monopolar attachment at meiosis I. Electron
4019
microscopy (EM) has shown that both sister kinetochores
indeed attach to microtubules (Goldstein, 1981; Parra et al.,
2004), excluding the possibility that inactivation of one sister
kinetochore results in monopolar attachment. An important
clue linking cohesin complexes to kinetochore orientation
came from the finding that the fission yeast rec8 mutant
undergoes equational, rather than reductional, division at
meiosis I (Watanabe and Nurse, 1999). Such bipolar
attachment of sister kinetochores at meiosis I also occurs in
the maize meiotic mutant absence of first division 1 (afd1),
which lacks the rec8 homolog Afd1 (W. Z. Cande, personal
communication). Subsequent analysis revealed that the
equational segregation at meiosis I depends on Rad21, which
relocates to the centromeres and establishes centromeric
cohesion if Rec8 is absent (Yokobayashi et al., 2003). This
suggests that monopolar attachment depends on Rec8, and that
Rad21 cannot substitute for it. ‘Equational meiosis I’ proceeds
with normal kinetics (Toth et al., 2000; Yokobayashi et al.,
2003), but there is no centromeric cohesion at anaphase I when
Rad21 is present instead of Rec8. Thus, centromeric protection
depends on the character of Rec8. Analysis of the localization
of cohesins around centromeres in fission yeast has revealed
that Rad21 complexes localize mainly to pericentromeric
heterochromatin, whereas Rec8 complexes localize to central
core regions as well as pericentromeric regions. The
enrichment of cohesins at the pericentromeric region depends
on the formation of heterochromatin at mitosis, providing
robust cohesion at centromeres that might be important for
faithful chromosome segregation (Bernard et al., 2001b;
Nonaka et al., 2002). Likewise, heterochromatin is also
required at meiosis for the enrichment of Rec8 at
pericentromeric regions, but not at the central core regions.
Interestingly, a lack of heterochromatin specifically abolishes
the centromeric cohesion that persists during anaphase of
meiosis I but does not affect monopolar attachment (Kitajima
et al., 2003b). A corollary is that the persisting cohesion at
meiosis I depends on pericentromeric Rec8 cohesins, whereas
the mono-orientation of sister kinetochores is carried out by
the central core rather than pericentromeric Rec8 complexes
(Fig. 3). From the DNA sequences of the centromere, Yanagida
and co-workers have predicted that the central core region (~10
kb) is likely to form structures that protrude from other regions
of the centromere (Fig. 3) (Takahashi et al., 1992). Moreover,
kinetochore proteins that interact with spindle microtubules
usually localize to the central core region, which suggests that
the spindle attachment interface lies in this region (Nakaseko
et al., 2001). One attractive model is that Rec8 creates monooriented protrusions at centromeres by establishing cohesion of
sister strands at the central core during DNA replication (Fig.
3) (Watanabe et al., 2001; Yokobayashi et al., 2003).
Unlike the centromeres of fission yeast and other eukaryotes,
the budding yeast centromere is unique in comprising a short
stretch of DNA (~125 bp) that is attached to a single
microtubule and lacks pericentromeric heterochromatin.
Knockout screening in budding yeast for genes that are
upregulated during meiosis has identified the meiosis-specific
kinetochore factor Mam1 (Toth et al., 2000). In mam1∆
cells, the meiosis I spindle fails to separate homologous
chromosomes but the meiosis II spindle can separate sister
chromatids. This suggests that Mam1 plays a specialized role
establishing monopolar attachment at meiosis I (Fig. 3).
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Journal of Cell Science 117 (18)
S. pombe
S. cerevisiae
S. pombe
centromere
Mitosis
Central core region
Pericentromeric
heterochromatin
region
Rad21
Monopolin
Rec8
Pericentromeric
heterochromatin
Spindle microtubule
Meiosis I
Fig. 3. Monopolar attachment at meiosis I. The centromeres of fission and budding yeast are
different. The requirement of Rec8 for monopolar attachment is obvious in fission yeast but
not in budding yeast, in which the ectopic expression of Scc1 can restore monopolar
attachment even in rec8∆ cells. Instead, monopolin complexes are required for monopolar
attachment in budding yeast.
Because centromeric protection is largely preserved in mam1∆
cells, this analysis suggests that monopolar attachment is
independent of the protection process.
A subsequent study revealed that a Mam1 protein complex
called monopolin includes at least two additional proteins,
Csm1 and Lrs4, both of which localize to the nucleolus in
vegetative cells but travel to kinetochores shortly before
meiosis I, in a complex with Mam1 (Rabitsch et al., 2003). The
localization of monopolin at kinetochores depends on the
activity of the polo-like kinase Cdc5; thus, budding yeast Cdc5
is required for establishing monopolar attachment (Clyne et al.,
2003; Lee and Amon, 2003). Monopolin does not appear to
be conserved in other organisms. Fission yeast contains a
protein related to Csm1, Pcs1. However, Pcs1 is required for
chromosome segregation during mitosis and meiosis II but not
for meiosis I (Rabitsch et al., 2003). Moreover, monopolar
attachment can be established in budding yeast rec8∆ cells
forced to express Scc1 during meiosis (Toth et al., 2000), which
contrasts with the observations in fission yeast (Yokobayashi
et al., 2003). The mechanisms for the establishment of
monopolar attachment thus seem to have diverged between
budding yeast and fission yeast. Further studies are required if
we are to formulate a generalized view of the regulation of
monopolar attachment in meiosis.
Centromeric protection throughout meiosis I
During meiosis I, sister chromatid cohesion is disrupted along
chromosome arms, whereas centromeric cohesion is protected.
Rec8 along the chromosome arms mostly disappears during
meiosis I, but centromeric Rec8 persists until meiosis II (Fig.
1). Several lines of evidence suggest that Rec8 along
chromosome arms is cleaved by separase, the same enzyme
that cleaves the mitotic cohesin Scc1/Rad21. In various
organisms, the inactivation of separase blocks homologue
segregation at meiosis I (Herbert et al., 2003; Siomos et al.,
2001; Terret et al., 2003). Similarly, in both budding yeast and
fission yeast, expression of a non-cleavable Rec8 mutant
lacking the separase target sequences also blocks their
segregation; indeed, abolishing recombination alleviates this
blockage (Buonomo et al., 2000; Kitajima et al., 2003a). These
results strongly suggest that the cleavage of Rec8 by separase
and the subsequent resolution of the chiasmata could be a
trigger for the segregation of homologues at meiosis I. When
the formation of arm cohesin complexes is disrupted by
depleting the arm-specific cohesin subunit Rec11 in fission
yeast, the hindrance of homologue separation by non-cleavable
Rec8 is alleviated whereas sister separation remains tightly
blocked. This blockage is released by inactivation of Psc3, a
major centromeric partner of Rec8 (Kitajima et al., 2003a).
Thus, these observations suggest that the cleavage of Rec8 in
the vicinity of centromeres is required for the initiation of
anaphase II. The securin accumulation-degradation cycle
operates not only at meiosis I but also at meiosis II, indicating
that separase is indeed activated at both divisions in meiosis
(Kitajima et al., 2003a; Salah and Nasmyth, 2000).
An obvious question concerns which molecules protect
centromeric Rec8 from degradation during meiosis I but not
during meiosis II. Budding yeast spo13 mutants show
significant defects in centromeric protection as well as in
monopolar orientation, largely undergoing equational division
at meiosis I (Klapholz and Esposito, 1980; Klein et al., 1999).
Moreover, ectopic expression of Spo13 together with Rec8
blocks sister chromatid separation at mitotic anaphase (Lee et
al., 2002; Shonn et al., 2002). These results suggest that
meiosis-specific Spo13 is involved in the protection of
centromeric Rec8. But Spo13 might not be a centromeric
protein and its homologues are not identified in other
organisms.
Recently, functional screening in fission yeast identified
shugoshin (Sgo1; Japanese for ‘guardian spirit’) as a Rec8
protector. The co-expression of Sgo1 and Rec8 in mitotic cells
blocks the degradation of centromeric Rec8 at anaphase,
resulting in inhibition of sister chromatid separation and
subsequent cell death. This protection is specific to Rec8
because, if Rad21 is predominant in cohesin complexes in the
cell, the forced expression of Sgo1 has little effect on mitotic
growth (Kitajima et al., 2004). Sgo1 is a meiosis-specific
Sister chromatid cohesion for meiosis
protein that is usually expressed during meiosis I. Deletion of
sgo1 leads to a defect in the persistence of centromeric Rec8
after anaphase I and subsequently results in random
segregation at meiosis II (Fig. 4). Independent knockout
screens in fission yeast and budding yeast also identified
the sgo1/SGO1 gene (Katis et al., 2004; Marston et al.,
2004; Rabitsch et al., 2004). Fission yeast Sgo1 localizes
to kinetochores, especially to the pericentromeric
heterochromatin regions, and associates with Rec8 complexes
in vivo. Because the heterochromatin-dependent enrichment of
Rec8 was independently shown to be important for persisting
centromeric cohesion, these results suggest that Sgo1 protects
pericentromeric Rec8 complexes from separase attack at the
onset of anaphase I. Sgo1 is degraded completely by meiosis
II, which is consistent with the notion that centromeric Rec8
is protected only during meiosis I and not during meiosis II
(Fig. 4) (Kitajima et al., 2004; Rabitsch et al., 2004).
Fission yeast has a paralogue of shugoshin, Sgo2, that
is ubiquitously expressed throughout its life cycle and
specifically localizes to kinetochores at metaphase during
mitosis and meiosis. sgo2∆ cells show chromosome instability
during proliferation and a substantial increase in the nondisjunction of homologues at meiosis I, indicating that Sgo2
plays a crucial role at kinetochores in chromosome segregation
in general (Kitajima et al., 2004; Rabitsch et al., 2004).
Although the precise molecular function of Sgo2 remains to be
addressed, it is likely that Sgo2 is a prototype of shugoshin,
from which Sgo1 diverged to become a specific protector of
Rec8. Budding yeast have a single shugoshin, Sgo1, which
behaves similarly to fission yeast Sgo1 and Sgo2 (Katis et al.,
2004; Kitajima et al., 2004; Marston et al., 2004). The
conservation of shugoshin in both yeasts is noteworthy. Careful
inspection of the databases, using conserved short stretches of
fungi shugoshins, revealed proteins with reasonably similar
regions in several multicellular organisms (Kitajima et al.,
2004). Strikingly, one such protein is Drosophila MEI-S332, a
previously identified kinetochore protein, mutations in which
lead to premature sister centromere separation in meiosis
(Kerrebrock et al., 1995; Lee and Orr-Weaver, 2001).
Consequently, MEI-S332 is now accepted to act as a Rec8
protector. MEI-S332 also has some role in mitosis, like
budding yeast Sgo1. Curiously, budding yeast, flies and worms
seem to have single shugoshin, whereas fission yeast, plants
and other animals have two (Table 1) (Kitajima et al., 2004).
In the latter organisms, shugoshin functions might be divided.
It remains to be seen exactly how shugoshin protects Rec8
from cleavage by separase, a problem that will be solved by
further biochemical and crystallographic analyses.
It would be interesting to know the precise localization of
budding yeast Sgo1, because the centromere structure in this
organism has diverged from that in fission yeast. The forced
expression of Rec8 in budding yeast does not block sister
separation during mitosis (despite the presence of Sgo1),
whereas co-expression of Rec8 with Spo13 does. Therefore,
budding yeast Sgo1 may be specifically activated or modified
to protect Rec8 during meiosis I, and this presumably depends
on Spo13. In fission yeast, the Bub1 checkpoint protein is
required for shugoshin (both Sgo1 and Sgo2) to localize to
Wild type
Rec8
Separase
Separase
4021
sgo1
Rec8
Sgo1
Metaphase I
Metaphase I
Anaphase I
Anaphase I
Metaphase II
Metaphase II
Anaphase II
Anaphase II
Fig. 4. Shugoshin protects centromeric Rec8 during meiosis I. At the onset of anaphase I, Sgo1 protects centromeric Rec8 from separase
cleavage; centromeric cohesion is thereby preserved until meiosis II. At the onset of anaphase II, the residual Rec8 is cleaved, which results in
the separation of sister chromatids. In sgo1∆ cells, all Rec8 is disrupted at meiosis I; therefore, sister chromatid cohesion is lost prior to meiosis
II. This brings about random segregation in meiosis II.
4022
Journal of Cell Science 117 (18)
kinetochores (Kitajima et al., 2004), which explains the
observation that centromeric Rec8 fails to persist throughout
meiosis I in bub1∆ cells (Bernard et al., 2001a).
Perspectives
We are now starting to understand the molecular details of
chromosome segregation during meiosis. Strikingly, the main
conserved players, cohesins and shugoshin, have ancestral
molecules that act during mitosis. Indeed, one would
intuitively think that meiosis evolved from mitosis not by the
abrupt emergence of a set of novel proteins but by a subtle
divergence of the mitotic apparatus, for example by gene
duplication. One of the mysteries of biology is why sexual
reproduction is so predominant in the eukaryotic world. A
likely explanation is that organisms must continuously evolve
to survive the continually changing environment on earth, for
which the mixing of genomes from two organisms has obvious
advantages. Whatever the answer, the essence of meiotic
devices should be found even in yeast, one of the most
primitive eukaryotic organisms.
Work in my lab is funded in part by grants from the Ministry of
Education, Science and Culture of Japan. I am grateful to members
of my lab for many discussions and in particular to Silke Hauf for
critical reading of the manuscript. I thank Richard Sever for extensive
editing of the text.
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