Human Asf1 regulates the flow of S phase histones during replicational stress.
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Human Asf1 regulates the flow of S phase histones during replicational stress. / Groth, Anja; Ray-Gallet, Dominique; Quivy, Jean-Pierre; Lukas, Jiri; Bartek, Jiri; Almouzni, Geneviève.
In: Molecular Cell, Vol. 17, No. 2, 2005, p. 301-11.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Human Asf1 regulates the flow of S phase histones during replicational stress.
AU - Groth, Anja
AU - Ray-Gallet, Dominique
AU - Quivy, Jean-Pierre
AU - Lukas, Jiri
AU - Bartek, Jiri
AU - Almouzni, Geneviève
N1 - Keywords: Animals; Cell Cycle Proteins; Cell Fractionation; Cell Line, Tumor; Chromatin; DNA Replication; Histones; Humans; Hydroxyurea; Macromolecular Substances; Molecular Chaperones; Nucleic Acid Synthesis Inhibitors; S Phase
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
U2 - 10.1016/j.molcel.2004.12.018
DO - 10.1016/j.molcel.2004.12.018
M3 - Journal article
C2 - 15664198
VL - 17
SP - 301
EP - 311
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 2
ER -
ID: 5013977