Regulation of Histone Deposition Proteins Asf1/Hir1 by Multiple DNA Damage Checkpoint Kinases in Saccharomyces cerevisiae

Replication blocks and DNA damage incurred during S phase activate the S-phase and intra-S-phase checkpoint responses, respectively, regulated by the Atrp and Chk1p checkpoint kinases in metazoans. In Saccharomyces cerevisiae, these checkpoints are regulated by the Atrp homologue Mec1p and the kinase Rad53p. A conserved role of these checkpoints is to block mitotic progression until DNA replication and repair are completed. In S. cerevisiae, these checkpoints include a transcriptional response regulated by the kinase Dun1p; however, dun1Δ cells are proficient for the S-phase-checkpoint-induced anaphase block. Yeast Chk1p kinase regulates the metaphase-to-anaphase transition in the DNA-damage checkpoint pathway via securin (Pds1p) phosphorylation. However, like Dun1p, yeast Chk1p is not required for the S-phase-checkpoint-induced anaphase block. Here we report that Chk1p has a role in the intra-S-phase checkpoint activated when yeast cells replicate their DNA in the presence of low concentrations of hydroxyurea (HU). Chk1p was modified and Pds1p was transiently phosphorylated in this response. Cells lacking Dun1p were dependent on Chk1p for survival in HU, and chk1Δ dun1Δ cells were defective in the recovery from replication interference caused by transient HU exposure. These studies establish a relationship between the S-phase and DNA-damage checkpoint pathways in S. cerevisiae and suggest that at least in some genetic backgrounds, the Chk1p/securin pathway is required for the recovery from stalled or collapsed replication forks.

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Reversible DNA damage checkpoint activation at the presenescent stage in telomerase‐deficient cells of Saccharomyces cerevisiae

Genes to Cells ◽

10.1111/gtc.12706 ◽

2019 ◽

Vol 24 (8) ◽

pp. 546-558 ◽

Cited By ~ 1

Author(s):

Atsuhiro Miura ◽

Eisuke Itakura ◽

Akira Matsuura

Keyword(s):

Saccharomyces Cerevisiae ◽

Dna Damage ◽

Dna Damage Checkpoint ◽

Checkpoint Activation

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The Saccharomyces cerevisiae DNA damage checkpoint is required for efficient repair of double strand breaks by non-homologous end joining

FEBS Letters ◽

10.1016/s0014-5793(00)01180-7 ◽

2000 ◽

Vol 467 (2-3) ◽

pp. 311-315 ◽

Cited By ~ 22

Author(s):

Maria-Angeles de la Torre-Ruiz ◽

Noel F. Lowndes

Keyword(s):

Saccharomyces Cerevisiae ◽

Dna Damage ◽

Double Strand Breaks ◽

Dna Damage Checkpoint ◽

End Joining ◽

Strand Breaks ◽

Non Homologous End Joining

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When heat casts a spell on the DNA damage checkpoints

Open Biology ◽

10.1098/rsob.140008 ◽

2014 ◽

Vol 4 (3) ◽

pp. 140008 ◽

Cited By ~ 8

Author(s):

Thomas Turner ◽

Thomas Caspari

Keyword(s):

Dna Damage ◽

Ataxia Telangiectasia ◽

Current Knowledge ◽

Dna Damage Checkpoint ◽

Ataxia Telangiectasia Mutated ◽

Patron Saint ◽

Checkpoint Kinases ◽

Dna Damage Checkpoints ◽

Heat Response ◽

Elevated Body Temperature

Peregrine Laziosi (1265–1345), an Italian priest, became the patron saint of cancer patients when the tumour in his left leg miraculously disappeared after he developed a fever. Elevated body temperature can cause tumours to regress and sensitizes cancer cells to agents that break DNA. Why hyperthermia blocks the repair of broken chromosomes by changing the way that the DNA damage checkpoint kinases ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) are activated is an unanswered question. This review discusses the current knowledge of how heat affects the ATR–Chk1 and ATM–Chk2 kinase networks, and provides a possible explanation of why homeothermal organisms such as humans still possess this ancient heat response.

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MEC3, MEC1, and DDC2Are Essential Components of a Telomere Checkpoint Pathway Required for Cell Cycle Arrest during Senescence in Saccharomyces cerevisiae

Molecular Biology of the Cell ◽

10.1091/mbc.02-02-0012 ◽

2002 ◽

Vol 13 (8) ◽

pp. 2626-2638 ◽

Cited By ~ 81

Author(s):

Shinichiro Enomoto ◽

Lynn Glowczewski ◽

Judith Berman

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Dna Damage ◽

Telomerase Activity ◽

Cellular Level ◽

Dna Damage Checkpoint ◽

Average Growth ◽

Progressive Decline ◽

Checkpoint Response ◽

Essential Components

When telomerase is absent and/or telomeres become critically short, cells undergo a progressive decline in viability termed senescence. The telomere checkpoint model predicts that cells will respond to a damaged or critically short telomere by transiently arresting and activating repair of the telomere. We examined the senescence of telomerase-deficient Saccharomyces cerevisiae at the cellular level to ask if the loss of telomerase activity triggers a checkpoint response. As telomerase-deficient mutants were serially subcultured, cells exhibited a progressive decline in average growth rate and an increase in the number of cells delayed in the G2/M stage of the cell cycle. MEC3, MEC1, andDDC2, genes important for the DNA damage checkpoint response, were required for the cell cycle delay in telomerase-deficient cells. In contrast, TEL1,RAD9, and RAD53, genes also required for the DNA damage checkpoint response, were not required for the G2/M delay in telomerase-deficient cells. We propose that the telomere checkpoint is distinct from the DNA damage checkpoint and requires a specific set of gene products to delay the cell cycle and presumably to activate telomerase and/or other telomere repair activities.

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DNA damage checkpoint and repair: from the budding yeast Saccharomyces cerevisiae to the pathogenic fungus Candida albicans

Computational and Structural Biotechnology Journal ◽

10.1016/j.csbj.2021.11.033 ◽

2021 ◽

Author(s):

Shuangyan Yao ◽

Yuting Feng ◽

Yan Zhang ◽

Jinrong Feng

Keyword(s):

Saccharomyces Cerevisiae ◽

Dna Damage ◽

Candida Albicans ◽

Budding Yeast ◽

Pathogenic Fungus ◽

Dna Damage Checkpoint ◽

Yeast Saccharomyces Cerevisiae

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A Role for Checkpoint Kinase-Dependent Rad26 Phosphorylation in Transcription-Coupled DNA Repair in Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.00822-09 ◽

2009 ◽

Vol 30 (2) ◽

pp. 436-446 ◽

Cited By ~ 14

Author(s):

Michael Taschner ◽

Michelle Harreman ◽

Yumin Teng ◽

Hefin Gill ◽

Roy Anindya ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Dna Damage ◽

Protein Synthesis ◽

Excision Repair ◽

Phosphorylation Site ◽

Coupling Factor ◽

Direct Role ◽

Checkpoint Kinases ◽

Nucleotide Excision ◽

New Protein

ABSTRACT Upon DNA damage, eukaryotic cells activate a conserved signal transduction cascade known as the DNA damage checkpoint (DDC). We investigated the influence of DDC kinases on nucleotide excision repair (NER) in Saccharomyces cerevisiae and found that repair of both strands of an active gene is affected by Mec1 but not by the downstream checkpoint kinases, Rad53 and Chk1. Repair of the nontranscribed strand (by global genome repair) requires new protein synthesis, possibly reflecting the involvement of Mec1 in the activation of repair genes. In contrast, repair of the transcribed strand by transcription-coupled NER (TC-NER) occurs in the absence of new protein synthesis, and DNA damage results in Mec1-dependent but Rad53-, Chk1-, Tel1-, and Dun1-independent phosphorylation of the TC-NER factor Rad26, a member of the Swi/Snf group of ATP-dependent translocases and yeast homologue of Cockayne syndrome B. Mutation of the Rad26 phosphorylation site results in a decrease in the rate of TC-NER, pointing to direct activation of Rad26 by Mec1 kinase. These findings establish a direct role for Mec1 kinase in transcription-coupled repair, at least partly via phosphorylation of Rad26, the main transcription-repair coupling factor.

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