Figure 8: 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.
