ArticleMolecular and cellular biology2013
Molecular basis of the essential s phase function of the rad53 checkpoint kinase.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- The DNA replication checkpoint targets the kinetochore to reposition DNA structure-induced replication damage to the nuclear periphery.Cell reports · 2025Article
- A Rfa1-MN-based system reveals new factors involved in the rescue of broken replication forks.PLoS genetics · 2025Article
- Stabilization of expandable DNA repeats by the replication factor Mcm10 promotes cell viability.Nature communications · 2024Article
- Article
- Prevalent and dynamic binding of the cell cycle checkpoint kinase Rad53 to gene promoters.eLife · 2022Article
- Rad53 arrests leading and lagging strand DNA synthesis via distinct mechanisms in response to DNA replication stress.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Functional interplay between the oxidative stress response and DNA damage checkpoint signaling for genome maintenance in aerobic organisms.Journal of microbiology (Seoul, Korea) · 2020Review
- PP4 phosphatase cooperates in recombinational DNA repair by enhancing double-strand break end resection.Nucleic acids research · 2019Article
- Mck1 defines a key S-phase checkpoint effector in response to various degrees of replication threats.PLoS genetics · 2019Article
- Multiple signaling kinases target Mrc1 to prevent genomic instability triggered by transcription-replication conflicts.Nature communications · 2018Article
- Mutations in the Non-Catalytic Subunit Dpb2 of DNA Polymerase Epsilon Affect the Nrm1 Branch of the DNA Replication Checkpoint.PLoS genetics · 2017Article
- Review
- Early Loss of Telomerase Action in Yeast Creates a Dependence on the DNA Damage Response Adaptor Proteins.Molecular and cellular biology · 2016Article
- Mec1, INO80, and the PAF1 complex cooperate to limit transcription replication conflicts through RNAPII removal during replication stress.Genes & development · 2016Article
- S phase block following MEC1ATR inactivation occurs without severe dNTP depletion.Biology open · 2015Article
- Increased and imbalanced dNTP pools symmetrically promote both leading and lagging strand replication infidelity.PLoS genetics · 2014Article
- Use of quantitative mass spectrometric analysis to elucidate the mechanisms of phospho-priming and auto-activation of the checkpoint kinase Rad53 in vivo.Molecular & cellular proteomics : MCP · 2014Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The essential yeast kinases Mec1 and Rad53, or human ATR and Chk1, are crucial for checkpoint responses to exogenous genotoxic agents, but why they are also required for DNA replication in unperturbed cells remains poorly understood. Here we report that even in the absence of DNA-damaging agents, the rad53-4AQ mutant, lacking the N-terminal Mec1 phosphorylation site cluster, is synthetic lethal with a deletion of the RAD9 DNA damage checkpoint adaptor. This phenotype is caused by an inability of rad53-4AQ to activate the downstream kinase Dun1, which then leads to reduced basal deoxynucleoside triphosphate (dNTP) levels, spontaneous replication fork stalling, and constitutive activation of and dependence on S phase DNA damage checkpoints. Surprisingly, the kinase-deficient rad53-K227A mutant does not share these phenotypes but is rendered inviable by additional phosphosite mutations that prevent its binding to Dun1. The results demonstrate that ultralow Rad53 catalytic activity is sufficient for normal replication of undamaged chromosomes as long as it is targeted toward activation of the effector kinase Dun1. Our findings indicate that the essential S phase function of Rad53 is comprised by the combination of its role in regulating basal dNTP levels and its compensatory kinase function if dNTP levels are perturbed.
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