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A CDK-regulated chromatin segregase promoting chromosome replication

DOI: 10.1038/s41467-021-25424-7 DOI Help

Authors: Erika Chacin (Ludwig-Maximilians-Universität) , Priyanka Bansal (Ludwig-Maximilians-Universität) , Karl-Uwe Reusswig (Max Planck Institute of Biochemistry) , Luis M. Diaz-Santin (University College London; Birkbeck College, London) , Pedro Ortega (University of Seville-CSIC) , Petra Vizjak (Ludwig-Maximilians-Universität) , Belen Gomez-Gonzalez (University of Seville-CSIC) , Felix Müller-Planitz (Technische Universität Dresden; Ludwig-Maximilians-Universität) , Andrés Aguilera (University of Seville-CSIC) , Boris Pfander (Max Planck Institute of Biochemistry) , Alan C. M. Cheung (University of Bristol; University College London; Birkbeck College, London) , Christoph F. Kurat (Ludwig-Maximilians-Universität)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 12

State: Published (Approved)
Published: September 2021
Diamond Proposal Number(s): 20287

Open Access Open Access

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.

Journal Keywords: Chromatin remodelling; DNA

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios II-Titan Krios II at Diamond

Added On: 09/09/2021 08:26

Documents:
s41467-021-25424-7.pdf

Discipline Tags:

Life Sciences & Biotech Genetics Structural biology

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)