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A growing list of empirical studies suggests that this rapid evolution has profound consequences on core biological processes. Here, we review recent studies that investigate the satellite DNA-mediated biology revealed by generating either inter-species hybrids or genotypes expressing divergent, satellite DNA-interacting proteins from a closely related species. The genetic incompatibilities that arise implicate chromosome segregation, DNA repair, the establishment of silent heterochromatin, and the spatial organization of chromosomes as essential processes vulnerable to the rapid evolution of satellite DNA. 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