Chromosome condensation mechanically primes the nucleus for mitosis

• Type: Other Publications
• Date: 2025

Authors

Nunes, V (Author) Other; Moura, M (Author) Other; Vareiro, D (Author) Other; Auduge, N (Author) Other; Borghi, N (Author) Other; J Ferreira (Author) FMUP

Other information

Authenticus ID: P-01A-1KB

DOI: 10.1101/2025.09.01.673438

Abstract (EN): <jats:title>Abstract</jats:title> <jats:p>Timely and accurate transition into mitosis is essential to preserve genome integrity and avoid chromosome segregation errors. This transition depends on spatial and temporal activity patterns of the cyclin B1-CDK1 complex, that eventually lead to nuclear envelope permeabilization (NEP) and irreversible mitotic commitment. How these patterns are orchestrated to ensure an error-free mitosis remains unclear. Here, using a combination of high-resolution imaging with cellular micromanipulation, we show that mitotic entry is controlled by the condensation of mitotic chromosomes, which generate a mechanical signal on the nuclear envelope during prophase. We further demonstrate how the nuclear envelope spatiotemporally integrates this mechanical signal to ensure the coordination between the cytoplasmic and nuclear events required for the transition into mitosis. Through the LINC complex, this chromosome-generated mechanical signal is relayed to the cytoplasm, ensuring timely nuclear translocation of cyclin B1. Simultaneously, SUN proteins transmit this signal directly to nuclear pore complexes independently of their role in the LINC complex, to regulate NEP and mitotic spindle assembly. We propose that irreversible mitotic commitment is controlled by a chromosome-dependent nuclear mechanism, that provides robust spatiotemporal coupling between chromosome condensation and mitotic entry, contributing to the maintenance of genome integrity.</jats:p>

Language: English

Type (Professor's evaluation): Scientific