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A CDK-regulated chromatin segregase promoting chromosome replication
DOI:
10.1038/s41467-021-25424-7
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

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:
Genetics
Structural biology
Life Sciences & Biotech
Technical Tags:
Microscopy
Electron Microscopy (EM)
Cryo Electron Microscopy (Cryo EM)