Growth, Differentiation and Sexuality

428 D. Zickler
ThemeannumberofLNspermid-pachytene
nucleus matches the species number of COs deduced
from genetic maps and/or chiasmata (review
in von Wettstein et al. 1984; Zickler and Kleckner
1999). LNs match also the COs and chiasmata location
along bivalent arms (e.g., Bojko 1989; Zickler
et al. 1992, for fungi). Like COs, LNs show both
intra-arm as well as inter-arm interference, as indicated
by their non-Poisson distribution (review
in Carpenter 1987). Also, the frequency of LNs
per micron length of SC is higher in small than
in larger chromosomes, as are the number of chiasmata
(review in Jones 1984; Zickler and Kleckner
1999). Mutants known to reduce the frequency
of meiotic exchanges and/or alter their distribution
alter also the number and location of the late
RNs in Drosophila and S. macrospora (Carpenter
1979; Zickler et al. 1992). The mismatch repair
Mlh1, Mlh3, Msh4 and Msh5p proteins are components
of LNs (Moens et al. 2002). A group of
proteins (Zip1p, Zip2p, Zip3p) specifically involved
in crossover maturation (but not in gene conversion)
are likely components of LNs in budding yeast
(Fung et al. 2004).
In contrast to LNs, ENs are distributed uniformly
and do not exhibit interference (e.g., Holm
et al. 1981 for C. cinereus). Their number per nucleus
is two to over 100 times the number of LNs.
The available evidence strongly suggests that ENs
represent recombinational interactions that are at
the DSBs stage or just later. First, their time of appearance,
along unsynapsed AEs or at the sites of
convergence between synapsing homologues, corresponds
to the transition of DSB into single-end
invasion intermediates formation (see Sect. III.).
By contrast, LNs appear later and are exclusively
associated with the SC central region.
Second, Rad51p assembles in large amounts
into ENs but not into LNs. Also, ENs are known
to occur in two stability classes, implying the occurrence
of a functionally transition that precedes
any obvious transition reflected in EM morphology
(review in Anderson et al. 2001).
Third, whereas LNs are of uniform appearance
within a given organism, ENs are notable for
their diversity of form, even in a given nucleus
(review in Zickler and Kleckner 1999). This diversity
is fully consistent with developmental progression
of a complex protein/DNA assembly through
a series of biochemical steps that are accompanied
by changes in both DNA and protein components.
However, the exact relationship between ENs and
LNs remains unknown.
VI. Meiotic Chromosome Segregation
or how to Resolve Sister-Chromatid
Cohesion in Two Steps
Successful execution of the two meiotic divisions
has three prerequisites. First, each pair of homologous
chromosomes must be connected by at least
one physical link achieved by crossover between
one sister chromatid of each homologue. Chiasmata
thus establish an inherent polarity that will direct
chromosome segregation: by staying together,
homologues are constrained such that their kinetochores
capture microtubules from opposite poles.
In addition, the link established by chiasmata plus
sister cohesion at the centromeric region counteracts
the pulling forces of the spindle, thereby generating
tension across the kinetochores and signaling
of a stable bipolar attachment. In the absence of chiasmata,
chromosomes are free to attach and travel
to either pole randomly (e.g., Moreau et al. 1985;
Storlazzi et al. 2003).
Second, sister kinetochores must orient to
the same spindle pole at division I, and to opposite
poles at division II. In budding yeast, the
meiosis-specific protein Mam1 collaborates with
the nucleolar proteins Csm1 and Lrs4 to ensure
co-orientation of sister kinetochores during
meiosis I. Their dissociation from kinetochores
during early anaphase I is likely to be part of the
events that allow sister kinetochores to bi-orient
during meiosis II (Toth et al. 2000; Rabitsch et al.
2003).
Third, cohesion must be released in two steps:
along arms, in order to permit the release of
chiasmata at metaphase I, and at centromeres at
metaphase II. Retention of centromeric cohesion
between sister chromatids beyond anaphase I is
critical for proper segregation of sister chromatids
during division II (review in Lee and Orr-Weaver
2001; Nasmyth 2001). Premature sister-chromatid
separation (e.g., in rec8 or spo76 mutants, see Klein
et al. 1999; van Heemst et al. 1999) or the inability
to separate sister chromatids in a timely fashion
(e.g., in spo12 and spo13 mutants, Katis et al. 2004)
lead to unequal chromosome segregation, and thus
chromosome imbalance in gametes. Chromosome
segregation is a central aspect of meiosis. Errors
in the transmission of chromosomes produce
aneuploid gametes/spores bearing too many or too
few chromosomes, the major cause of infertility in
all organisms, including fungi (review in Lee and
Orr-Weaver 2001).