Human Asf1 regulates the flow of S phase histones during replicational stress.

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

SN - 1097-2765

VL - 17

SP - 301

EP - 311

JO - Molecular Cell

JF - Molecular Cell

IS - 2

ER -