Growth, Differentiation and Sexuality

430 D. Zickler
B. Other Proteins Important for Sister-
Chromatid Cohesion and Segregation
Besides cohesins, several proteins have essential
roles in generating or maintaining sister cohesion
during meiosis. Five proteins have been implicated
in protecting centromeric cohesion during
division I.
1. The MEI-S332 and ORD proteins of D.
melanogaster are required to maintain
sister cohesion until anaphase II (Lee and Orr-
Weather 2001; Balicky et al. 2002). A protein related
to MEI-S332, called Sgo1 (for “shugoshin”,
which means “protector” in Japanese), binds
to centromeric DNA during both meiotic divisions
in fission and budding yeasts. Sgo1 is necessary
both for protecting centromeric Rec8p
fromseparase,andforpropersistercentromere
disjunction at division II (Kitajima et al. 2004).
Through its regulation of microtubules, Sgo1
may also influence the spindle checkpoint,
and is thus a crucial link between centromere
cohesion and kinetochore/microtubule interaction
(Salic et al. 2004). Sgo1 function is
likely conserved, as orthologues are found in
N. crassa and M. grisea (Rabitsch et al. 2004).
2. The conserved Bub1 spindle-checkpoint
kinase is also required for both the retention
of Rec8 at centromeres and their correct
disjunction at division II (Bernard et al. 2001).
3. The budding yeast meiosis-specific protein
Spo13 (which so far has no known orthologue)
is necessary to prevent sister kinetochore biorientation
during metaphase I, by facilitating
the recruitment of Mam1 to kinetochores
(review in Katis et al. 2004).
The complex composed of Scc2/Mis4/Rad9 and
Scc4, required for the loading of the cohesin complex
onto chromosomes, is also implied in sister
cohesion during meiosis. C. cinereus rad9 mutants
are impaired in cohesion, homologous pairing,
and in chromosome condensation (Seitz et al.
1996; Cummings et al. 2002). However, as the rad9
mutant still shows a partial defect in homologous
pairing in a spo22/msh5 background (thus, in the
absence of a sister chromatid), the role of Rad9p in
homologous pairing may not entirely derive from
its role in sister cohesion (Cummings et al. 2002).
The Spo76/BIMD/Pds5 protein family members
are conserved components of the basic
chromosome structure that are recruited from the
mitotic cycle and functionally adapted for use in
the meiotic program (van Heemst et al. 1999, 2001).
They are likely needed for the morphological transformations
in chromosome structure that lead to
condensed metaphase chromosomes, as shown
by the fact that S. macrospora and budding yeast
spo76/pds5 mutants show defects in both chromosome
cohesion and condensation (van Heemst
et al. 1999; Hartman et al. 2000; Panizza et al. 2000).
Although bound to the same chromosome sites
as the cohesin complex, Spo76/Pds5 is not part of
the cohesin complex, and Scc1/Mcd1 is needed for
chromosomal localization of Pds5 (Hartman et al.
2000, Panizza et al. 2000). Aside from their role
in chromosome morphogenesis, they are also involved
in cell cycle progression: human orthologue
AS3 is a possible tumor suppressor (Geck et al.
2000), and A. nidulans BIMD is a negative regulator
of normal mitotic cell cycle progression, with a G1
arrest when over-expressed (Denison et al. 1993;
van Heemst et al. 2001). All mutants are hypersensitive
to DNA damage, and Spo76p is also required
for meiotic inter-homologue recombination, likely
at post-initiation stages (van Heemst et al. 1999).
The bimD6 mutant shows reduced homologous
recombination but normal intra-chromosomal
recombination, suggesting that BIMD/Spo76 is not
involved in the enzymology of recombinational
repair per se (van Heemst et al. 2001). The specific
defects of the S. macrospora spo76-1 mutant at
both mitotic prometaphase and meiotic zygotene,
with cohesion and condensation coordinately
affected on a regional basis, suggest that Spo76p
plays a crucial role at this critical chromosome
transition point for both divisions. Also, Spo76-
GFP makes stronger lines during meiotic prophase
(Fig. 20.4) than during mitotic prophase, showing
that Spo76p is used to reinforce the sister cohesion
along meiotic axes, which fits with the mutant
phenotypes. Maintenance of meiotic chromosome
axes integrity and formation of the SC are also
dependent on Spo76p (van Heemst et al. 1999).
During meiosis, Spo76/Pds5p likely plays the role
of a spring-clip, allowing local destabilization at
sites of recombination and chiasma formation,
while maintaining chromosome axis integrity
elsewhere (Storlazzi et al. 2003).
VII. From Meiosis to Sporulation
Genetically defined mating types impose developmental
constraints in most mycelial fungi, and