Year: 2026
Type: article
Abstract: Why eukaryotic genomes are universally divided among multiple chromosomes remains an unresolved question. Although yeast and mouse cells can tolerate chromosomal fusions without impairing viability, we show here that chromosome length in mammalian cells is constrained by a biophysical limit governed by spindle geometry. Using engineered mouse cells carrying fused chromosomes of defined sizes, we identify ~308 Mb as the maximal length tolerated for faithful mitosis. Chromosomes exceeding this threshold disrupt segregation, leading to daughter cell re-coalescence and polyploidization. Aurora B kinase regulates this process by modulating spindle elongation; its inhibition induces mitotic failure even in chromosome configurations within the tolerated threshold of ~308 Mb. These findings explain the structural basis for genome fragmentation in animals and reveal a general mechanism linking chromosome size, spindle dynamics, and genome stability.
Source: Molecular Systems Biology
Institutions: Chinese Academy of Sciences, Peking University, University of Chinese Academy of Sciences, Institute of Zoology, State Key Laboratory of Stem Cell and Reproductive Biology, Beijing Institute for Stem Cell and Regenerative Medicine, Peking University Third Hospital, Sun Yat-sen University
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $7,990
Funders: National Natural Science Foundation of China, Chinese Academy of Sciences, Ministry of Science and Technology of the People's Republic of China, National Health Commission of the People's Republic of China, Beijing Municipal Natural Science Foundation, Institute of Zoology, Chinese Academy of Sciences, National Key Research and Development Program of China
OpenAlex ID: W7124260312