Document Detail


Human Asf1 regulates the flow of S phase histones during replicational stress.
MedLine Citation:
PMID:  15664198     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Maintenance of chromosomal integrity requires tight coordination of histone biosynthesis with DNA replication. Here, we show that extracts from human cells exposed to replication stress display an increased capacity to support replication-coupled chromatin assembly. While in unperturbed S phase, hAsf1 existed in equilibrium between an active form and an inactive histone-free pool, replication stress mobilized the majority of hAsf1 into an active multichaperone complex together with histones. This active multichaperone complex was limiting for chromatin assembly in S phase extracts, and hAsf1 was required for the enhanced assembly activity in cells exposed to replication stress. Consistently, siRNA-mediated knockdown of hAsf1 impaired the kinetics of S phase progression. Together, these data suggest that hAsf1 provides the cells with a buffering system for histone excess generated in response to stalled replication and explains how mammalian cells maintain a critical "active" histone pool available for deposition during recovery from replication stresses.
Authors:
Anja Groth; Dominique Ray-Gallet; Jean-Pierre Quivy; Jiri Lukas; Jiri Bartek; Geneviève Almouzni
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular cell     Volume:  17     ISSN:  1097-2765     ISO Abbreviation:  Mol. Cell     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-24     Completed Date:  2005-03-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  301-11     Citation Subset:  IM    
Affiliation:
Institute of Cancer Biology, The Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle Proteins / genetics,  metabolism*
Cell Fractionation
Cell Line, Tumor
Chromatin / metabolism
DNA Replication*
Histones / metabolism*
Humans
Hydroxyurea / metabolism
Macromolecular Substances
Molecular Chaperones / genetics,  metabolism
Nucleic Acid Synthesis Inhibitors / metabolism
S Phase / physiology*
Chemical
Reg. No./Substance:
0/ASF1A protein, human; 0/Cell Cycle Proteins; 0/Chromatin; 0/Histones; 0/Macromolecular Substances; 0/Molecular Chaperones; 0/Nucleic Acid Synthesis Inhibitors; 127-07-1/Hydroxyurea

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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