Abstract

Centromeres are the DNA loci responsible for the faithful partitioning of eukaryotic chromosomes. The elaborate protein assembly, called the kinetochore complex, organized at the centromere is responsible for attaching sister chromosomes to the mitotic spindle, thus ensuring their equal segregation during cell division. Centromeres in nearly all eukaryotes are regional centromeres- long DNA segments with no consensus sequence elements- that are established epigenetically. Members of the budding yeast lineage are a stark exception. Their chromosomes harbor point centromeres- very short centromeres with three well defined sequence elements- that are genetically determined. The yeast centromere chromatin engenders a positive supercoil, presumably due to a nucleosome containing a variant of the histone H3. Yeast harbors a selfish plasmid whose stability is comparable to that of the chromosomes of its host. The plasmid achieves this fidelity of segregation with the help of two partitioning proteins and a partitioning locus called STB (for stability). Strikingly, the chromatin at STB is also positively supercoiled. When STB function is inactivated, its topology shifts to standard negative supercoiling. The magnitudes of the CEN and STB induced positive supercoiling are comparable. The topological equivalence of CEN and STB , along with other functional similarities between the two, are consistent with the notion that the non-standard point centromere had its origin in the partitioning locus of an ancestral plasmid.