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

Kats, Ellen S.; Albuquerque, Claudio P.; Zhou, Huilin; Kolodner, Richard D.

doi:10.1073/pnas.0511102103

Cited by 31 publications

(48 citation statements)

References 43 publications

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“…The cell cycle distribution was followed using the budding index, which uses the bud morphology of normal log-phase cells to identify cells in G 1 phase (no bud), S phase (small bud), and G 2 /M phase (large bud). We also counted cells with aberrant morphology, which typically consist of cells with grossly elongated or multiple buds and have been observed in strains with alterations in the timing of cell cycle transitions, DNA replication defects, and uncoupling of replication defects from checkpoint responses (56,64,73,74). We observed decreased proportions of G 1 -and S-phase cells, along with an increased fraction of cells with aberrant morphologies in strains where the rnh203⌬ mutation was combined with the asf1⌬, esc2⌬, mgs1⌬, mph1⌬, mre11⌬, rad50⌬, rad52⌬, or xrs2⌬ mutation ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The budding index, defined as the ratio of the number of individuals bearing buds to the total cell number, was determined microscopically, with individual cells bearing buds being counted as one cell (56). Cells were grown in YPD medium to log phase, sonicated, and examined by light microscopy, and the numbers of single cells, small-budded cells (bud smaller than onethird of the mother cell), large-budded cells (bud equal to or larger than one-third of the mother cell), and other cells (cells with protruded or multiple buds) were recorded.…”

Section: Methodsmentioning

confidence: 99%

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A Saccharomyces cerevisiae RNase H2 Interaction Network Functions To Suppress Genome Instability

Allen-Soltero

Martı́nez

Putnam

et al. 2014

Molecular and Cellular Biology

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Errors during DNA replication are one likely cause of gross chromosomal rearrangements (GCRs). Here, we analyze the role of RNase H2, which functions to process Okazaki fragments, degrade transcription intermediates, and repair misincorporated ribonucleotides, in preventing genome instability. The results demonstrate that rnh203 mutations result in a weak mutator phenotype and cause growth defects and synergistic increases in GCR rates when combined with mutations affecting other DNA metabolism pathways, including homologous recombination (HR), sister chromatid HR, resolution of branched HR intermediates, postreplication repair, sumoylation in response to DNA damage, and chromatin assembly. In some cases, a mutation in RAD51 or TOP1 suppressed the increased GCR rates and/or the growth defects of rnh203⌬ double mutants. This analysis suggests that cells with RNase H2 defects have increased levels of DNA damage and depend on other pathways of DNA metabolism to overcome the deleterious effects of this DNA damage.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Saccharomyces cerevisiae RNase H2 Interaction Network Functions To Suppress Genome Instability

Allen-Soltero

Martı́nez

Putnam

et al. 2014

Molecular and Cellular Biology

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“…These data suggest that DNA damage generated by perturbation of the replisome requires Rtt109 and H3 Lys-56-Ac for survival. Many of these phenotypes are shared by mutants that lack Asf1, an H3/H4 histone binding chaperone (13,(35)(36)(37). This phenotypic similarity was recently explained by the finding that Asf1 is also required for H3 Lys-56-Ac (13).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Histone H3 Lysine 56 Acetylation in Schizosaccharomyces pombe

Xhemalçe

Miller

Driscoll

et al. 2007

Journal of Biological Chemistry

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In Saccharomyces cerevisiae, acetylation of lysine 56 (Lys-56) in the globular domain of histone H3 plays an important role in response to genotoxic agents that interfere with DNA replication. However, the regulation and biological function of this modification are poorly defined in other eukaryotes. Here we show that Lys-56 acetylation in Schizosaccharomyces pombe occurs transiently during passage through S-phase and is normally removed in G 2 . Genotoxic agents that cause DNA double strand breaks during replication elicit a delay in deacetylation of histone H3 Lys-56. In addition, mutant cells that cannot acetylate Lys-56 are acutely sensitive to genotoxic agents that block DNA replication. Moreover, we show that Spbc342.06cp, a previously uncharacterized open reading frame, encodes the functional homolog of S. cerevisiae Rtt109, and that this protein acetylates H3 Lys-56 both in vitro and in vivo. Altogether, our results indicate that both the regulation of histone H3 Lys-56 acetylation by its histone acetyltransferase and histone deacetylase and its role in the DNA damage response are conserved among two distantly related yeast model organisms.Histone acetylation corresponds to the covalent attachment of an acetyl group to a lysine residue. This modification is mediated by histone acetyltransferases (HATs) 7 and is reversible as the acetyl group can be removed through the action of histone deacetylases (HDACs). Lysine acetylation on histones is best characterized for its role in transcriptional regulation, but evidence for a crucial function during replication and DNA damage tolerance is accumulating (1-3). Indeed, newly synthesized histones that are deposited throughout the genome during replication are transiently acetylated at several lysine residues (4, 5). These include sites of acetylation in the N-terminal tails of both histones H3 and H4 (6 -8). Recently, two novel sites of acetylation in the globular domains of newly synthesized histone molecules were uncovered by mass spectrometry of Saccharomyces cerevisiae histones, lysine 91 (Lys-91) of histone H4 (9) and lysine 56 (Lys-56) of histone H3 (10 -15).H3 Lys-56 acetylation (H3 Lys-56-Ac) shows a particular link between DNA replication and DNA damage tolerance. In budding yeast, this modification occurs concomitantly with DNA replication as virtually all the newly synthesized histone H3 molecules deposited throughout the genome are Lys-56-acetylated, whereas in the G 2 /M-phase of the cell cycle the vast majority of H3 Lys-56 is deacetylated (11,(15)(16)(17). However, in response to DNA breaks during replication, histone H3 Lys-56 acetylation is maintained in a DNA damage checkpointdependent manner. In S. cerevisiae this modification plays a key role in surviving DNA damage as cells in which histone H3 cannot be acetylated at Lys-56 are acutely sensitive to genotoxic agents that interfere with DNA replication (10 -13).The deacetylation of H3 Lys-56 requires the Sir2-related HDACs Hst3 and Hst4 (16,17). Hst3 and Hst4 are cell cycles regulated with peak...

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“…Several studies using this approach have demonstrated that there are eight pathways for suppressing these chromosomal aberrations, while six pathways promote GCR formation. The suppression mechanisms include cell cycle checkpoints [7][8][9][10][11][12], post-replication [13,14] and mismatch repair [15,16], recombination pathways, an anti-de novo telomere addition mechanism [17,18], chromatin assembly factors [11,19], mechanisms that prevent end-to-end chromosome fusions [17,18,20] and a pathway detoxifying reactive oxygen species [14,21,22]. In contrast, the promoters of GCRs include telomerase-related factors [17,23], a mitotic checkpoint network [24], the Rad1-Rad10 endonuclease [25], non-homologous end-joining proteins including Lig4 and Nej1 [17], a pathway generating inappropriate recombination via sumoylation and the Srs2 helicase [13] and the Bre1 ubiquitin ligase [13].…”

Section: Introductionmentioning

confidence: 99%

Smc5–Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications

et al. 2008

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Translocations in chromosomes alter genetic information. Although the frequent translocations observed in many tumors suggest the altered genetic information by translocation could promote tumorigenesis, the mechanisms for how translocations are suppressed and produced are poorly understood. The smc6-9 mutation increased the translocation class gross chromosomal rearrangement (GCR). Translocations produced in the smc6-9 strain are unique because they are nonreciprocal and dependent on break-induced replication (BIR) and independent of non-homologous end joining. The high incidence of translocations near repetitive sequences such as δ sequences, ARS, tRNA genes, and telomeres in the smc6-9 strain indicates that Smc5-Smc6 suppresses translocations by reducing DNA damage at repetitive sequences. Synergistic enhancements of translocations in strains defective in DNA damage checkpoints by the smc6-9 mutation without affecting de novo telomere addition class GCR suggest that Smc5-Smc6 defines a new pathway to suppress GCR formation.

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

Cited by 31 publications

References 43 publications

A Saccharomyces cerevisiae RNase H2 Interaction Network Functions To Suppress Genome Instability

A Saccharomyces cerevisiae RNase H2 Interaction Network Functions To Suppress Genome Instability

Regulation of Histone H3 Lysine 56 Acetylation in Schizosaccharomyces pombe

Smc5–Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications

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