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PMID: 11025658 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Temporally coordinated assembly and disassembly of replication factories in the absence of DNA synthesis.

Nature cell biology ·Vol. 2 ·No. 10 ·2000-10-00 ·Pages 686-94

Dimitrova DS, Gilbert DM

Abstract

Here we show that exposure of aphidicolin-arrested Chinese hamster ovary (CHO) cells to the protein-kinase inhibitors 2-aminopurine or caffeine results in initiation of replication at successively later-replicating chromosomal domains, loss of the capacity to synthesize DNA at earlier-replicating sites, release of Mcm2 proteins from chromatin, and redistribution of PCNA and RPA from early- to late-replicating domains in the absence of detectable elongation of replication forks. These results provide evidence that, under conditions of replicational stress, checkpoint controls not only prevent further initiation but may also be required to actively maintain the integrity of stalled replication complexes.

MeSH Terms
2-Aminopurine/pharmacology Animals Aphidicolin/pharmacology CHO Cells Caffeine/pharmacology Chromatin/metabolism Chromosomes/metabolism Cricetinae DNA Replication DNA-Binding Proteins/metabolism Minichromosome Maintenance Complex Component 2 Nuclear Proteins/metabolism Proliferating Cell Nuclear Antigen/metabolism Protein Kinase Inhibitors Replication Origin Replication Protein A S Phase Time Factors
Chemicals
Chromatin DNA-Binding Proteins Nuclear Proteins Proliferating Cell Nuclear Antigen Protein Kinase Inhibitors Replication Protein A Aphidicolin Caffeine 2-Aminopurine Minichromosome Maintenance Complex Component 2
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Dimitrova D S
Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, 750 East Adams Street, Syracuse, New York 13210, USA.
Gilbert D M
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1465-7392
DOI
10.1038/35036309
Published
2000-10-00
Pages
686-94
Language
English
Region
England
NLM ID
100890575
PMCID
PMC1255923
Subset
IM
Grants
NIGMS NIH HHS · R01 GM057233 · United States
NIGMS NIH HHS · GM57233-01 · United States
External Links
PubMed source DOI: 10.1038/35036309 PMC Full Text View journal details
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