Chromosome compaction is triggered by an autonomous DNA-binding module within condensin.

The compaction of chromatin into mitotic chromosomes is essential for faithful transmission of the genome during cell division. In eukaryotes, chromosome morphogenesis is regulated by the condensin complex, though the exact mechanism used to target condensin to chromatin and initiate condensation is not understood. Here, we reveal that condensin contains an intrinsically disordered region (IDR) that modulates its association with chromatin in early mitosis and exhibits phase separation. We describe DNA-binding motifs within the IDR that, upon deletion, inflict striking defects in chromosome condensation and segregation, ill-timed condensin turnover on chromatin, and cell death. Importantly, we demonstrate that the condensin IDR can impart cell cycle regulatory functions when transferred to other subunits within the complex, indicating its autonomous nature. Collectively, our study unveils the molecular basis for the initiation of chromosome condensation in early mitosis and how this process ultimately promotes genomic stability and faultless cell division. [Display omitted] • The condensin complex is the main regulator of chromosome condensation in mitosis • Condensin contains an essential intrinsically disordered protein region (IDR) • Purified condensin IDR exhibits phase separation and binds DNA substrates • IDR mutations lead to defective chromosome condensation and segregation During mitosis, chromatin is reorganized into compact chromosomes by the highly dynamic condensin complex. Pastic et al. find that condensin possesses a conformationally flexible, disordered region that is essential for its dynamic association with chromatin. Mutations in this region lead to severe defects in chromosome condensation, segregation, and cell proliferation. [ABSTRACT FROM AUTHOR]