<i>Saccharomyces cerevisiae</i>
            chromatin-assembly factors that act  during DNA replication function in the maintenance of genome stability

Myung, Kyungjae; Pennaneach, Vincent; Kats, Ellen S.; Kolodner, Richard D.

doi:10.1073/pnas.1232239100

Cited by 130 publications

(125 citation statements)

References 71 publications

(147 reference statements)

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“…Therefore, evidence presented here (Figs. 1, 2) and elsewhere (Tyler et al 1999;Myung et al 2003;Prado et al 2004;Ramey et al 2004) are all consistent with a role for Asf1 in genome stability that is restricted to S phase.…”

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

confidence: 58%

“…Although Asf1 is not required for activation of the S-phase checkpoint (Emili et al 2001), Asf1 directly interacts with the DNA damage/replication checkpoint kinase Rad53 in a manner regulated by checkpoint activation (Emili et al 2001;Hu et al 2001). Also, asf1⌬ cells display multiple phenotypes suggesting elevated levels of spontaneous DNA damage, including increased phosphorylation of Rad53, Rad9, Mrc1, and H2A (Hu et al 2001;Schwartz et al 2003;Prado et al 2004;Ramey et al 2004); accumulation of Ddc2-GFP foci; and increased rates of gross chromosomal rearrangements and sister chromatid exchanges (Myung et al 2003;Prado et al 2004;Ramey et al 2004). However, the cause of this spontaneous DNA damage and the molecular nature of the link between Asf1 and the DNA replication machinery had been unknown.…”

mentioning

confidence: 99%

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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 supporting

confidence: 58%

mentioning

confidence: 99%

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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“…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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“…Yeast asf1 mutants have elevated rates of sister chromatid exchange, mutation, and spontaneous DNA damage foci [94,97]. Similarly, CAF-1 and asf1 mutants have elevated rates of gross chromosomal rearrangements [98]. However, it has yet to be determined whether this genomic instability upon inactivation of CAF-1 and Asf1 is a consequence of failure to perform their role in chromatin disassembly / assembly during DNA repair or during DNA replication.…”

Section: The Consequences Of Failure To Assemble and Disassemble Chromentioning

confidence: 99%

Chromatin disassembly and reassembly during DNA repair

Linger

Tyler

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Current research is demonstrating that the packaging of the eukaryotic genome together with histone proteins into chromatin is playing a fundamental role in DNA repair and the maintenance of genomic integrity. As is well established to be the case for transcription, the chromatin structure dynamically changes during DNA repair. Recent studies indicate that the complete removal of histones from DNA and their subsequent reassembly onto DNA accompanies DNA repair. This review will present evidence indicating that chromatin disassembly and reassembly occur during DNA repair and that these are critical processes for cell survival after DNA repair. Concomitantly, candidate proteins utilized for these processes will be highlighted.

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Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability

Cited by 130 publications

References 71 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

Chromatin disassembly and reassembly during DNA repair

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