Human Asf1 Regulates the Flow of S Phase Histones during Replicational Stress

Groth, Anja; Ray-Gallet, Dominique; Quivy, Jean‐Pierre; Lukáš, Jiří; Bártek, Jiří; Almouzni, Geneviève

doi:10.1016/j.molcel.2004.12.018

Cited by 246 publications

(291 citation statements)

References 38 publications

(2 reference statements)

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“…We note that in human cells, replication-coupled chromatin assembly is required for completion of S phase (Nelson et al 2002;Hoek and Stillman 2003;Ye et al 2003). Furthermore, one human isoform of Asf1 is required for formation of the facultative heterochromatin that forms during cellular senescence (Zhang et al 2005) and for progression through S phase (Groth et al 2005). Future experiments will be important for determining how Asf1 isoforms in human cells contribute to S-phase progression.…”

Section: Changes In Stalled Replisome Architecture In the Absence Of mentioning

confidence: 89%

Histone deposition protein Asf1 maintains DNA replisome integrity and interacts with replication factor C

Franco¹,

Lam²,

Burgers³

et al. 2005

Genes Dev.

127

125

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Chromatin assembly and DNA replication are temporally coupled, and DNA replication in the absence of histone synthesis causes inviability. Here we demonstrate that chromatin assembly factor Asf1 also affects DNA replication. In budding yeast cells lacking Asf1, the amounts of several DNA replication proteins, including replication factor C (RFC), proliferating cell nuclear antigen (PCNA), and DNA polymerase (Pol ), are reduced at stalled replication forks. In contrast, DNA polymerase ␣ (Pol ␣) accumulates to higher than normal levels at stalled forks in asf1⌬ cells. Using purified, recombinant proteins, we demonstrate that RFC directly binds Asf1 and can recruit Asf1 to DNA molecules in vitro. We conclude that histone chaperone protein Asf1 maintains a subset of replication elongation factors at stalled replication forks and directly interacts with the replication machinery.[Keywords: Chromatin assembly; histone deposition; DNA replication; genome stability] Supplemental material is available at http://www.genesdev.org. In eukaryotes, DNA is assembled into a nucleoprotein complex called chromatin. The fundamental repeating unit of chromatin is the nucleosome, which consists of 146 bp of DNA wrapped around an octamer of core histone proteins, comprised of two H2A/H2B dimers flanking an inner (H3/H4) 2 tetramer. In vivo, histone deposition can occur by DNA replication-coupled or replication-independent mechanisms (for review, see Franco and Kaufman 2004). In either case, histone deposition is mediated by specialized assembly proteins. The best characterized replication-coupled chromatin assembly factor is chromatin assembly factor-1 (CAF-1), an evolutionarily conserved protein complex that binds histone H3 and H4 and delivers them to replicating DNA through an interaction with proliferating cell nuclear antigen (PCNA), the DNA polymerase processivity protein (for review, see Asf1, another evolutionarily conserved histone chaperone, functions during both replication-coupled and replication-independent chromatin assembly. Asf1 bound to histones H3/H4 stimulates histone deposition by CAF-1 in vitro (Tyler et al. 1999;Sharp et al. 2001), and Asf1 physically interacts with the p60/Cac2 subunit of CAF-1 (Tyler et al. 2001;Krawitz et al. 2002;Mello et al. 2002). In yeast, Asf1 and the Hir proteins directly interact and function together to promote heterochromatic gene silencing (Kaufman et al. 1998;Sharp et al. 2001;Sutton et al. 2001;Krawitz et al. 2002). Consistent with a role in multiple deposition pathways, Asf1 copurifies with both CAF-1 and Hir protein complexes in human cell extracts (Tagami et al. 2004).Asf1 also contributes to genome stability during S phase in a manner distinct from both CAF-1 and the Hir proteins. Unlike yeast cells lacking CAF-1 or Hir proteins, cells lacking Asf1 are sensitive to the DNA synthesis inhibitor hydroxyurea (HU) and the DNA topoisomerase I inhibitor camptothecin (CPT), and display synthetic genetic interactions with DNA synthesis genes including the initiation/elongation factor C...

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Section: Changes In Stalled Replisome Architecture In the Absence Of mentioning

confidence: 89%

Histone deposition protein Asf1 maintains DNA replisome integrity and interacts with replication factor C

Franco¹,

Lam²,

Burgers³

et al. 2005

Genes Dev.

127

125

View full text Add to dashboard Cite

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“…Yeast Asf1p is required for heterochromatin-mediated silencing of telomeres and mating loci and has histone deposition activity in vitro (67,116,121,127). Yeast Asf1p is also required for histone eviction and subsequent replacement at transcribed genes (1,66,111), and also plays a role in DNA replication-coupled chromatin assembly (44,51,86,110,127). Yeast Hir1p and Hir2p share several biological and biochemical properties with Asf1p.…”

Section: Chromosome Condensation Is Driven By Histone Chaperones Hiramentioning

confidence: 99%

Remodeling of chromatin structure in senescent cells and its potential impact on tumor suppression and aging

Adams

2007

Gene

162

135

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Cellular senescence is an important tumor suppression process, and a possible contributor to tissue aging. Senescence is accompanied extensive changes in chromatin structure. In particular, many senescent cells accumulate specialized domains of facultative heterochromatin, called Senescence Associated Heterochromatin Foci (SAHF), which are thought to repress expression of proliferationpromoting genes, thereby contributing to senescence-associated proliferation arrest. This article reviews our current understanding of the structure, assembly and function of these SAHF at a cellular level. The possible contribution of SAHF to tumor suppression and tissue aging is also critically discussed.

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“…S. cerevisiae mutants lacking Asf1 exhibit sensitivity to a wider range of DNA-damaging agents and have a slow growth phenotype compared with CAF-I-defective mutants (8), suggesting that CAF-I and RCAF may have some distinct functions. Asf1 has also been implicated in the buffering of free histones during DNA-damageinduced cell cycle arrest (20) as well as chromatin disassembly at certain loci (21).…”

mentioning

confidence: 99%

Checkpoint functions are required for normal S-phase progression in Saccharomyces cerevisiae RCAF- and CAF-I-defective mutants

Kats

Albuquerque

Zhou

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The chromatin-assembly factor I (CAF-I) and the replication-coupling assembly factor (RCAF) complexes function in chromatin assembly during DNA replication and repair and play a role in the maintenance of genome stability. Here, we have investigated their role in checkpoints and S-phase progression. FACS analysis of mutants lacking Asf1 or Cac1 as well as various checkpoint proteins indicated that normal rates of S-phase progression in asf1 mutants have a strong requirement for replication checkpoint proteins, whereas normal S-phase progression in cac1 mutants has only a weak requirement for either replication or DNA-damage checkpoint proteins. Furthermore, asf1 mutants had high levels of Ddc2.GFP foci that were further increased in asf1 dun1 double mutants consistent with a requirement for checkpoint proteins in S-phase progression in asf1 mutants, whereas cac1 mutants had much lower levels of Ddc2.GFP foci that were not increased by a dun1 mutation. Our data suggest that RCAF defects lead to unstable replication forks that are then stabilized by replication checkpoint proteins, whereas CAF-I defects likely cause different types of DNA damage.chromatin assembly ͉ DNA-damage response ͉ DNA replication ͉ genome instability

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Human Asf1 Regulates the Flow of S Phase Histones during Replicational Stress

Cited by 246 publications

References 38 publications

Histone deposition protein Asf1 maintains DNA replisome integrity and interacts with replication factor C

Histone deposition protein Asf1 maintains DNA replisome integrity and interacts with replication factor C

Remodeling of chromatin structure in senescent cells and its potential impact on tumor suppression and aging

Checkpoint functions are required for normal S-phase progression in Saccharomyces cerevisiae RCAF- and CAF-I-defective mutants

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