Centromere: A Trojan horse for genome stability

Centromeres play a key role in the maintenance of genome stability to prevent carcinogenesis and diseases. They are specialized chromosome loci essential to ensure faithful transmission of genomic information across cell generations by mediating the interaction with spindle microtubules. Nonetheless, while fulfilling these essential roles, their distinct repetitive composition and susceptibility to mechanical stresses during cell division render them susceptible to breakage events. In this review, we delve into the present understanding of the underlying causes of centromere fragility, from the mechanisms governing its DNA replication and repair, to the pathways acting to counteract potential challenges. We propose that the centromere represents a “Trojan horse” exerting vital functions that, at the same time, potentially threatens whole genome stability.