Simona Giunta and Hironori Funabiki
Significance
The centromere is a highly specialized genomic locus playing a critical role in chromosome segregation during cell division and is made of characteristic repetitive DNA sequences. Due to their repetitive nature, it has been difficult to study the organization of human centromeres. Here, we present a way to monitor stability of the human centromeres using chromosome-orientation fluorescent in situ hybridization and superresolution microscopy. We show that the centromere-specific histone variant CENP-A and the centromere-associated proteins CENP-C and CENP-T contribute to maintenance of centromere integrity and present evidence of centromere disregulation in cancer and during cellular senescence, which is related to aging. Our study reveals the existence of a centromere-specific mechanism to organize the repetitive structure and prevent human centromeres from suffering illegitimate rearrangements.