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A CDK-regulated chromatin segregase promoting chromosome replication

By Erika Chacin, Priyanka Bansal, Karl-Uwe Reusswig, Luis Diaz-Santin, Pedro Ortega, Petra Vizjak, Belen Gomez-Gonzalez, Felix Mueller-Planitz, Andres Aguilera, Boris Pfander, Alan Cheung, Christoph Kurat

Posted 22 Nov 2020
bioRxiv DOI: 10.1101/2020.11.20.390914

The replication of chromosomes during S phase is critical for cellular and organismal function. Replicative stress can result in genome instability, which is a major driver of cancer. Yet how chromatin is made accessible during eukaryotic DNA synthesis is poorly understood. Here, we report the identification of a novel class of chromatin remodeling enzyme, entirely distinct from classical SNF2-ATPase family remodelers. Yta7 is a AAA+-ATPase that assembles into ~ 1 MDa hexameric complexes capable of segregating histones from DNA. Yta7 chromatin segregase promotes chromosome replication both in vivo and in vitro. Biochemical reconstitution experiments using purified proteins revealed that enzymatic activity of Yta7 is regulated by S phase-forms of Cyclin-Dependent Kinase (S-CDK). S-CDK phosphorylation stimulates ATP hydrolysis by Yta7, promoting nucleosome disassembly and chromatin replication. Our results present a novel mechanism of how cells orchestrate chromatin dynamics in co-ordination with the cell cycle machinery to promote genome duplication during S phase.

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