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- Structure and Function of the Conserved Core of Histone Depo...Structure and Function of the Conserved Core of Histone Deposition Protein Asf1
Current Biology, Volume 13, Issue 24, 16 December 2003, Pages 2148-2158
Sally M Daganzo, Jan P Erzberger, Wendy M Lam, Emmanuel Skordalakes, Rugang Zhang, Alexa A Franco, Steven J Brill, Peter D Adams, James M Berger and Paul D Kaufman
SummaryThe evolutionarily conserved, N-terminal 155 amino acids of histone deposition protein Asf1 are functional in vitro and in vivo. This core region of Asf1 adopts a compact immunoglobulin-fold structure with distinct surface characteristics, including a Hir protein binding region required for gene silencing.
Summary | Full Text | PDF (580 kb) - Identification of human Asf1 chromatin assembly factors as s...Identification of human Asf1 chromatin assembly factors as substrates of Tousled-like kinases
Current Biology, Volume 11, Issue 13, 10 July 2001, Pages 1068-1073
Herman H.W. Silljé and Erich A. Nigg
SummaryFirst described in , Tousled-like kinases (Tlks) are highly conserved in both plants and animals. In plants, Tousled kinase is essential for proper flower and leaf development, but no direct functional link to any other plant gene product has yet been established . Likewise, the role of Tlks in animals is unknown. In human cells, two structurally similar Tlks, Tlk1 and Tlk2, were recently shown to be cell cycle-regulated kinases with maximal activities during S phase . Here, we report the identification of two human homologs of the chromatin assembly factor Asf1 (anti-silencing function 1) as physiological substrates of Tlks. We show that human Asf1 proteins are phosphorylated by Tlks both in vivo and in vitro. Furthermore, Asf1 proteins are phosphorylated during S phase, when Tlks are maximally active. Conversely, Asf1 proteins are dephosphorylated upon the activation of the DNA replication checkpoint, concomitant with the rapid inactivation of Tlks. These data indicate that Tlk family members regulate chromatin assembly during DNA replication, and they suggest a plausible explanation for the pleiotropic developmental defects of plant mutants .
Summary | Full Text | PDF (344 kb) - Histone H3.1 and H3.3 Complexes Mediate Nucleosome Assembly ...Histone H3.1 and H3.3 Complexes Mediate Nucleosome Assembly Pathways Dependent or Independent of DNA Synthesis
Cell, Volume 116, Issue 1, 9 January 2004, Pages 51-61
Hideaki Tagami, Dominique Ray-Gallet, Geneviève Almouzni and Yoshihiro Nakatani
SummaryDeposition of the major histone H3 (H3.1) is coupled to DNA synthesis during DNA replication and possibly DNA repair, whereas histone variant H3.3 serves as the replacement variant for the DNA-synthesis-independent deposition pathway. To address how histones H3.1 and H3.3 are deposited into chromatin through distinct pathways, we have purified deposition machineries for these histones. The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and HIRA, that we show are necessary to mediate DNA-synthesis-dependent and -independent nucleosome assembly, respectively. Notably, these complexes possess one molecule each of H3.1/H3.3 and H4, suggesting that histones H3 and H4 exist as dimeric units that are important intermediates in nucleosome formation. This finding provides new insights into possible mechanisms for maintenance of epigenetic information after chromatin duplication.
Summary | Full Text | PDF (377 kb) - …more
Copyright © 2005 Elsevier Inc.. All rights reserved.
Molecular Cell, Volume 17, Issue 2, 301-311, 21 January 2005
doi:10.1016/j.molcel.2004.12.018
Article
Human Asf1 Regulates the Flow of S Phase Histones during Replicational Stress
Anja Groth1, Dominique Ray-Gallet2, 3, Jean-Pierre Quivy2, 3, Jiri Lukas1, Jiri Bartek*, 1, 
and Geneviève Almouzni*, 2,
1 Institute of Cancer Biology, The Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
2 Institut Curie, Section de Recherche UMR 218 du CNRS, 26 rue d'Ulm, 75248 Paris Cedex 05, France
Correspondence: Jiri Bartek, +45 35 25 73 57 (phone), +45 35 25 77 21 (fax); and Geneviève Almouzni3 These authors contributed equally to this work.
Summary
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.
