A chromatinized origin reduces the mobility of ORC and MCM through interactions and spatial constraint.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
23 10 2023
Historique:
received: 15 06 2023
accepted: 13 10 2023
medline: 27 10 2023
pubmed: 24 10 2023
entrez: 23 10 2023
Statut: epublish

Résumé

Chromatin replication involves the assembly and activity of the replisome within the nucleosomal landscape. At the core of the replisome is the Mcm2-7 complex (MCM), which is loaded onto DNA after binding to the Origin Recognition Complex (ORC). In yeast, ORC is a dynamic protein that diffuses rapidly along DNA, unless halted by origin recognition sequences. However, less is known about the dynamics of ORC proteins in the presence of nucleosomes and attendant consequences for MCM loading. To address this, we harnessed an in vitro single-molecule approach to interrogate a chromatinized origin of replication. We find that ORC binds the origin of replication with similar efficiency independently of whether the origin is chromatinized, despite ORC mobility being reduced by the presence of nucleosomes. Recruitment of MCM also proceeds efficiently on a chromatinized origin, but subsequent movement of MCM away from the origin is severely constrained. These findings suggest that chromatinized origins in yeast are essential for the local retention of MCM, which may facilitate subsequent assembly of the replisome.

Identifiants

pubmed: 37872142
doi: 10.1038/s41467-023-42524-8
pii: 10.1038/s41467-023-42524-8
pmc: PMC10593741
doi:

Substances chimiques

Origin Recognition Complex 0
Nucleosomes 0
Cell Cycle Proteins 0
DNA 9007-49-2
Minichromosome Maintenance Proteins EC 3.6.4.12
Saccharomyces cerevisiae Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6735

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Humberto Sánchez (H)

Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.

Zhaowei Liu (Z)

Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.

Edo van Veen (E)

Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.

Theo van Laar (T)

Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.

John F X Diffley (JFX)

Chromosome Replication Laboratory, Francis Crick Institute, London, United Kingdom.

Nynke H Dekker (NH)

Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands. n.h.dekker@tudelft.nl.

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Classifications MeSH