Mitotic chromosomes are self-entangled and disentangle through a Topoisomerase II-dependent two stage exit from mitosis

• DOI: 10.1101/2022.10.15.511838
• Publication Date: 2022-10-16T10:05:13Z
• Authors: Erica M. Hildebrand; Kirill Polovnikov; Bastiaan Dekker; Yu Liu; Denis L. Lafontaine; A. Nicole Fox; Ying Li; Sergey V. Venev; Leonid Mirny; Job Dekker
• Keywords: Interphase

SUMMARY The topological state of chromosomes determines their mechanical properties, dynamics, and function. Recent work indicated that interphase are largely free entanglements. Here, we use Hi-C, polymer simulations multi-contact 3C, propose that, in contrast, mitotic self-entangled. We explore how a self-entangled is converted into an unentangled during exit. Most entanglements removed anaphase/telophase, with remaining ones early G1, Topoisomerase II-dependent process. Polymer models suggest two-stage disentanglement pathway: first, decondensation condensin loops produces entropic forces bias II activity towards decatenation. At the second stage, released, formation new prevented by lower activity, allowing establishment territorial G1 chromosomes. When not removed, experiment models, normal cannot be acquired.