Centromeres are dismantled by foundational meiotic proteins Spo11 and Rec8

Meiotic processes are potentially dangerous to genome stability and could be disastrous if activated in proliferative cells. Here we show that two key meiosis-defining proteins, the double strand break-forming topoisomerase Spo11 and the meiotic cohesin Rec8, can dismantle centromeres. This dismantlement is normally observable only in mutant cells lacking the telomere bouquet, which provides a nuclear microdomain conducive to centromere reassembly(1); however, overexpression of Spo11 or Rec8 leads to levels of centromere dismantlement that cannot be countered by the bouquet. Specific nucleosome remodeling factors mediate centromere dismantlement by Spo11 and Rec8. Remarkably, ectopic expression of either protein in proliferating cells leads to mitotic kinetochore loss in both fission yeast and human cells. Hence, while centromeric chromatin has been characterized as extraordinarily stable, Spo11 and Rec8 challenge this stability, and may jeopardize kinetochores in the increasing number of cancers known to express meiotic proteins.