Growth, Differentiation and Sexuality

Fig. 20.2. Meiotic recombination. Shown are two homologous
DNA duplexes (of the four involved in the process),
one in grayand one in black.Meioticrecombination initiates
with a double-strand break (DSB)inoneduplex.Processing
of the ends results in single-stranded tails (SEI).Asinglestranded
tail then invades the homologous duplex. Repair
synthesis (dotted lines)resultsinadoubleHollidayjunction
(DHJ) that can be resolved to generate either crossing-over
(right) or noncrossover (left) products. Crossovers will result
as 4 : 4 asci (four wild-type spores, black, and four mutant
ascospores, white) whereas noncrossovers will result
in 2 : 6 (or 6 : 2) asci in S. macrospora heterozygous crosses
(shown above the corresponding drawings)
the aberrant segregation occurred at the pyridoxin
mutant site, and not as a consequence of aberrant
chromosome segregation.
However, most progress in our understanding
of the conversion of DSBs into CO and NCO has
been associated with the development of physical
assays of recombination in completely synchronous
budding yeast meiocytes (e.g., Padmore
et al. 1991; Schwacha and Kleckner 1995; Hunter
and Kleckner 2001). These approaches have defined
several key events occurring from leptotene
to diplotene. DSB formation is followed by the sequential
appearance of two stable strand exchange
intermediates (Fig. 20.2). One strand at one end of
theDSBundergoesstableexchangewithonestrand
of the homologous DNA duplex to give a singleend
invasion intermediate (SEI), which will be converted
to double Holliday junction (DHJ; Fig. 20.2).
DHJs will in turn be converted into CO products
at late pachytene (Schwacha and Kleckner 1995;
Allers and Lichten 2001; Hunter and Kleckner 2001;
Börner et al. 2004).
In budding yeast, DHJs were shown to be precursors
specifically of COs, eliminating the hypothesis
that the CO/NCO differentiation is made by alternate
resolution of Holliday junctions (Allers and
Lichten 2001). Also, the CO versus NCO decision is
Fungal Meiosis 421
made prior to, or concomitant with formation of
SEIs (Börner et al. 2004). Allers and Lichten (2001)
and Börner et al. (2004) proposed therefore that
CO/NCO control might be imposed as soon as DSBs
are engagedinnascentinteractions with the homologous
DNA duplex region of their homologue partner
(Fig. 20.2, and detailed drawings in Bishop and
Zickler 2004). Moreover, recent studies of the endonuclease
Mus81 indicate that, in addition to DHJ
resolution, some COs may be formed by the processing
of non-DHJ intermediates. Interestingly,
these latter COs do not show interference (review
in Hollingsworth and Brill 2004). The MUS81 pathway
accounts for a relatively minor fraction of COs
in budding yeast, and likely in both S. macrospora
and N. crassa, accordingtothepresenceofMSH4
and MSH5, encoding meiosis-specific MutS homologues
required to promote COs. By contrast, the
MUS81 pathway is responsible for most, if not all,
of the COs in fission yeast and C. elegans (review
in Hollingsworth and Brill 2004). Thus, the decision
of which CO pathway to use appears to vary
between organisms.
The considerable recent progress made in elucidating
the meiotic recombination process is the
extension of an almost 80-year-long development
of studies on recombination, in which mycelial
fungi played a central and often pioneering role.
Detailed analyses of CO and NCO events, together
with stimulating models, allowed the discovery of
key steps of the process (for excellent reviews, see
Esser and Kuenen 1967; Catcheside 1977; Whitehouse
1982; Rossignol et al. 1988; Nicolas and Petes
1994).
C. Meiotic Exchanges Are Highly Regulated
An additional, prominent feature of meiotic recombination
is the tight regulation of both the number
and distribution of exchanges along and among
chromosomes. Although a large number of recombinational
interactions are initiated, only a selected
subset is designated for maturation into COs, the
remaining interactions maturing primarily or exclusively
into inter-homologue NCOs. In the absence
of any regulation, COs and their cytological
counterparts, chiasmata and recombination nodules
(RNs; see Sect. V.), should be randomly distributed
among and along chromosomes. Analysis
of their distribution in several organisms shows
clearly that their distribution is non-random, as
reflected by three main features.