The chromosome periphery (CP) is a complex network of proteins and RNAs that coats the outer surface of mitotic chromosomes. Although other structural features of mitotic chromosomes, such as centromeres and telomeres, have been well-studied, CP composition and function remains largely enigmatic. In this study (Stamatiou et al., 2023), Paola Vagnarelli and colleagues analyse the mitotic chromosome proteome and identify a novel CP protein, CCDC86 (also known as cyclon). The authors show that CCDC86 is enriched in the CP during mitosis and that this localisation requires Ki-67, a core organising protein essential to the formation of the CP. siRNA-mediated depletion of CCDC86 causes abnormalities, such as increased formation and size of nucleolar-derived foci (NDFs), aggregates of CP proteins. Interestingly, these aggregates contain Ki-67, which is not usually found in NDFs, suggesting that CCDC86 might regulate Ki-67 localisation. CCDC86-depleted cells consequently display increased errors in chromosome alignment, altered spindle length and increased apoptosis. Finally, CCDC86 has previously been associated with the oncogene MYC to drive aggressive lymphoma growth. Here, the authors show that CCDC86 expression is regulated by MYCN in neuroblastoma cells and thus might have prognostic and therapeutic potential. Overall, this study further elucidates the composition of the CP and the importance of CCDC86 in mitosis.
