Centromeres are dismantled by foundational meiotic proteins Spo11 and Rec8

• Published in: Nature (London) Vol. 591; no. 7851; pp. 671 - 676
• Main Authors: Hou, Haitong, Kyriacou, Eftychia, Thadani, Rahul, Klutstein, Michael, Chapman, Joseph H., Cooper, Julia Promisel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25-03-2021; Nature Publishing Group
• Subjects: 13; 13/106; 14; 631/337/100/102; 631/337/103/90; 631/80/103/90; 631/80/641/2002; Cell Cycle Proteins - metabolism; Cell Line; Cell Proliferation; Centromere - chemistry; Centromere - metabolism; Centromeres; Chromatin; Chromatin - chemistry; Chromatin - metabolism; Chromosomes; Cohesin; Control; Deoxyribonucleic acid; Dismantling; DNA; Ectopic expression; Endodeoxyribonucleases - metabolism; Genomes; Genotype & phenotype; Humanities and Social Sciences; Humans; Kinetochores; Kinetochores - metabolism; Meiosis; multidisciplinary; Phosphoproteins - metabolism; Prophase; Proteins; Recombinant proteins; Schizosaccharomyces; Schizosaccharomyces pombe Proteins - metabolism; Science; Science (multidisciplinary); Stability; Telomerase; Telomeres; Varieties; Yeast; Yeasts; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-021-03279-8

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 topoisomerase Spo11 (which forms double-strand breaks) and the meiotic cohesin Rec8, can dismantle centromeres. This dismantlement is normally observable only in mutant cells that lack the telomere bouquet, which provides a nuclear microdomain conducive to centromere reassembly
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; however, overexpression of Spo11 or Rec8 leads to levels of centromere dismantlement that cannot be countered by the bouquet. Specific nucleosome remodelling factors mediate centromere dismantlement by Spo11 and Rec8. Ectopic expression of either protein in proliferating cells leads to the loss of mitotic kinetochores 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 cancers that express meiotic proteins.
The meiotic proteins Spo11 and Rec8, which ensure meiotic recombination and reductional chromosome segregation, have additional activities that challenge centromere stability by promoting centromeric nucleosome remodelling in both fission yeast and human cells.