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Cdc48/VCP Promotes Chromosome Morphogenesis by Releasing Condensin from Self-Entrapment in Chromatin.

Thattikota Y, Tollis S, Palou R, Vinet J, Tyers M, D'Amours D

Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128, succursale Centre-ville, Montréal, QC H3C 3J7, Canada; Ottawa Institute of Systems Biology, Department of Cellular and Molecular Medicine, University of Ottawa, Roger Guindon Hall, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.

The morphological transformation of amorphous chromatin into distinct chromosomes is a hallmark of mitosis. To achieve this, chromatin must be compacted and remodeled by a ring-shaped enzyme complex known as condensin. However, the mechanistic basis underpinning condensin's role in chromosome remodeling has remained elusive. Here we show that condensin has a strong tendency to trap itself in its own reaction product during chromatin compaction and yet is capable of interacting with chromatin in a highly dynamic manner in vivo. To resolve this apparent paradox, we identified specific chromatin remodelers and AAA-class ATPases that act in a coordinated manner to release condensin from chromatin entrapment. The Cdc48 segregase is the central linchpin of this regulatory mechanism and promotes ubiquitin-dependent cycling of condensin on mitotic chromatin as well as effective chromosome condensation. Collectively, our results show that condensin inhibition by its own reaction product is relieved by forceful enzyme extraction from chromatin.

Mol. Cell 2018;69(4):664-676.e5.

Pubmed ID: 29452641

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