Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

MEIOSIS
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localized at the kinetochores in meiosis I, but we do not know in any detail how
these proteins work. They are removed from kinetochores after meiosis I, so that
in meiosis II the sister-chromatid pairs can be bi-oriented on the spindle as they
are in mitosis.
Second, crossovers generate a strong physical linkage between homologs,
allowing their bi-orientation at the equator of the spindle—much like cohesion
between sister chromatids is important for their bi-orientation in mitosis (and
meiosis II). Crossovers hold homolog pairs together only because the arms of
the sister chromatids are connected by sister-chromatid cohesion (see Figure
17–58A).
Third, cohesion is removed in anaphase I only from chromosome arms and
not from the regions near the centromeres, where the kinetochores are located.
The loss of arm cohesion triggers homolog separation at the onset of anaphase I.
This process depends on APC/C activation, which leads to securin destruction,
separase activation, and cohesin cleavage along the arms (see Figure 17–38).
Cohesins near the centromeres are protected from separase in meiosis I by
a kinetochore-associated protein called shugoshin (from the Japanese word
for “guardian spirit”). Shugoshin acts by recruiting a protein phosphatase that
removes phosphates from centromeric cohesins. Cohesin phosphorylation is
normally required for separase to cleave cohesin; thus, removal of this phosphorylation
near the centromere prevents cohesin cleavage. Sister-chromatid pairs
therefore remain linked through meiosis I, allowing their correct bi-orientation
on the spindle in meiosis II. Shugoshin is inactivated after meiosis I. At the onset
of anaphase II, APC/C activation triggers centromeric cohesin cleavage and sisterchromatid
separation—much as it does in mitosis. Following anaphase II, nuclear
envelopes form around the chromosomes to produce four haploid nuclei, after
which cytokinesis and other differentiation processes lead to the production of
haploid gametes.
Crossing-Over Is Highly Regulated
Crossing-over has two distinct functions in meiosis: it helps hold homologs
together so that they are properly segregated to the two daughter nuclei produced
by meiosis I, and it contributes to the genetic diversification of the gametes that
are eventually produced. As might be expected, therefore, crossing-over is highly
regulated: the number and location of double-strand breaks along each chromosome
is controlled, as is the likelihood that a break will be converted into a crossover.
On average, the result of this regulation is that each pair of human homologs
is linked by about two or three crossovers (Figure 17–59).
Although the double-strand breaks that occur in meiosis I can be located
almost anywhere along the chromosome, they are not distributed uniformly: they
cluster at “hot spots,” where the DNA is accessible, and occur only rarely in “cold
spots,” such as the heterochromatin regions around centromeres and telomeres.
10 µm
Figure 17–59 Crossovers between
homologs in the human testis. In
these immunofluorescence micrographs,
antibodies have been used to stain the
synaptonemal complexes (red), the
centromeres (blue), and the sites of
crossing-over (green). Note that all of the
bivalents have at least one crossover and
none have more than four. (Modified from
A. Lynn et al., Science 296:2222–2225,
2002. With permission from AAAS.)