A CDK-regulated chromatin segregase promoting chromosome replication

Erika Chacin, Priyanka Bansal, Karl-Uwe Reusswig, Luis M. Diaz-Santin, Pedro Ortega, Petra Vizjak, Belen Gómez-González, Felix Müller-Planitz, Andrés Aguilera, Boris Pfander, Alan C. M. Cheung and Christoph F. Kurat ()
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Erika Chacin: Ludwig-Maximilians-Universität
Priyanka Bansal: Ludwig-Maximilians-Universität
Karl-Uwe Reusswig: DNA Replication and Genome Integrity
Luis M. Diaz-Santin: University College London
Pedro Ortega: University of Seville-CSIC
Petra Vizjak: Ludwig-Maximilians-Universität
Belen Gómez-González: University of Seville-CSIC
Felix Müller-Planitz: Ludwig-Maximilians-Universität
Andrés Aguilera: University of Seville-CSIC
Boris Pfander: DNA Replication and Genome Integrity
Alan C. M. Cheung: University College London
Christoph F. Kurat: Ludwig-Maximilians-Universität

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract 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 characterization of a chromatin remodeling enzyme—Yta7—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. The Yta7 chromatin segregase promotes chromosome replication both in vivo and in vitro. Biochemical reconstitution experiments using purified proteins revealed that the 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 mechanism for how cells orchestrate chromatin dynamics in co-ordination with the cell cycle machinery to promote genome duplication during S phase.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25424-7

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DOI: 10.1038/s41467-021-25424-7

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