Figure 6: Divergent kleisin
subunits of cohesin specify
distinct mechanisms that tether
and release meiotic
chromosomes. Establishment of
cohesion (top). REC-8 and COH-3/4
cohesins load onto chromosomes
at different times, using shared and
separate loading factors, and
establish sister chromatid cohesion
by different mechanisms. Cohesion
mediated by REC-8 is established
after pre-meiotic DNA replication
and before the onset of meiosis. In
contrast, bound COH-3/4 cohesins
require the DNA double strand
breaks made by the
meiosis-specific SPO-11
endonuclease to trigger cohesion.
The sole other example of
replication-independent cohesion
establishment occurs in mitotically
proliferating yeast that suffer DNA
damage.
Release of cohesion (bottom
cartoon). In C. elegans, a single
asymmetrically positioned
crossover forms between each pair
of homologous chromosomes, and
the site of the crossover, rather
than a centromere, determines
where sister chromatid cohesion
will be released during the meiotic
divisions. In the cartoon, sisters of
one homolog are red and orange,
and sisters of the other are light
and dark blue. After
recombination is complete, the
chromosomes are restructured
around the crossover to form a
cruciform structure. Just prior to
the first meiotic division, SCC is
released at the short arm to allow
homologs to separate. SCC
persists at the long arm until just
before the second meiotic division,
when it is released to allow sisters
to separate.
REC-8 and COH-3/4 cohesins
(represented schematically by
orange and green ovals) appear
distributed all along sister
chromatids in recombined
homologous chromosomes (see
Figure 5) and in chromosomes
restructured around the crossover.
Separase-independent removal of
REC-8 and COH-3/4 cohesins from
reciprocal chromosomal territories
then occurs in prometaphase, long
before the first meiotic division.
Confocal micrographs of cruciform
chromosomes stained with
antibodies to the axis protein
HTP-3 and kleisin subunits REC-8 or
COH-3/4 show the selective
removal of REC-8 cohesin from the
short arms and its persistence
along the long arms. The
reciprocal pattern occurs for
COH-3/4 cohesins, removal from
the long arm and persistence on
the short arm. The pattern of
kleisin removal in prometaphase is
consistent with the phenotypes
caused by null mutations. Loss of
rec-8 causes all sisters to separate
prematurely in the first meiotic
division. In contrast, loss of coh-3/4
causes random segregation of
homologous chromosomes. Our
work suggests that COH-3/4 must
be destroyed by separase to allow
homologs to separate and then
REC-8 must be destroyed to allow
sisters to separate.