During cell division, chromosomes invariably segregate before the cleavage furrow ingresses to partition the cell. Chromosomes that obstruct the furrow could block cytokinesis leading to altered cell ploidy, a defect common in cancer. Most cellular checkpoints minimize chromosome mis-segregation by delaying cell cycle progression until the chromosomes are replicated and bi-oriented to the spindle poles. However, this strategy may not be compatible with embryonic development, during which the timing of cell divisions must be closely coordinated. In C. elegans embryos, somatic cells with chromosome or spindle abnormalities can initiate cytokinesis (1-3). However, the cleavage furrow did not regress in embryos containing chromatin bridges induced by topoisomerase II (
top-2) RNAi (4). To address whether this phenomenon of sustained furrow integrity is seen in other chromomsome mis-segregation events, we inactivated several genes essential for segregation. While most conditions that generate chromatin bridges do not trigger cleavage furrow regression, the loss of the condensin complexes does. Condensin I and II contain the Structural Maintenance of Chromosome 2 and 4 homologs, MIX-1 and SMC-4, and additional subunits unique to each complex. The disruption of a shared subunit of condensin I and II was sufficient to induce both chromosome mis-segregation and furrow regression. We found that disruption specific to each condensin complex could functionally separate these two defects. Loss of condensin II caused chromosome mis-segregation, while mutations in condensin I did not. Furrow regression is only seen when chromatin bridges occur in the condensin I mutants, suggesting that condensin I may be required to sustain furrow integrity. Condensin I is highly enriched on chromatin bridges. Surprisingly, condensin I normally localizes to the spindle midzone, and disruption of the spindle midzone via
spd-1 deficiency recapitulates this condensin I mutant phenotype. Together our data support the presence of a pathway, resembling the abscission checkpoint (5), which prevents furrow regression in the presence of chromatin bridges in C. elegans embryos.
1. M Brauchle et al. Curr Biol 13, 819 (2003). 2. AH Holway et al. J Cell Biol 172, 999 (2006). 3. SE Encalada et al. Mol Biol Cell 16, 1056 (2005). 4. JN Bembenek et al. Curr Biol 20, 259 (2010). 5. P Steigemann et al. Cell 136, 473 (2009).