Cells with defective heterochromatin display increased rates of chromosome loss and an elevated frequency of lagging chromosomes on late anaphase spindles (Allshire et al. 1995; Ekwall et al. 1995, 1996). Consequently, mutants are sensitive to microtubule destabilising drugs such as thiabendazole. This indicates that loss of heterochromatin from centromeres affects centromere function. These defects arise because Swi6 is somehow required to recruit the cohesin complex over the outer repeats. The cohesin complex is required for tight physical cohesion of sister chro-matids. In the absence of Swi6 (and Clr4), subunits of cohesin (Rad21 and Psc3) dissociate from centromeric outer repeats, and cohesion at centromeres, but not chromosome arms, is lost (Bernard and Allshire 2002; Bernard et al. 2001; Nonaka et al. 2002). Thus, any mutations affecting the formation of heterochromatin at centromeres ultimately lead to defective chromosome segregation. Fission yeast cells that lack centromeric heterochromatin remain viable because cohesion along chromosome arms is unaffected and is sufficient to sustain reasonable levels of chromosome segregation in an organism with just three chromosomes. Consistent with this, cells with a mild lesion in the Rad21 cohesin subunit require Swi6/hetero-chromatin for viability (Bernard et al. 2001).
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