Cell cycle progression in the presence of irreparable DNA damage is controlled by a Mec1‐ and Rad53‐dependent checkpoint in budding yeast

@article{Neecke1999CellCP,
  title={Cell cycle progression in the presence of irreparable DNA damage is controlled by a Mec1‐ and Rad53‐dependent checkpoint in budding yeast},
  author={H Neecke and Giovanna Lucchini and Maria Pia Longhese},
  journal={The EMBO Journal},
  year={1999},
  volume={18}
}
We studied the response of nucleotide excision repair (NER)‐defective rad14Δ cells to UV irradiation in G1 followed by release into the cell cycle. Only a subset of checkpoint proteins appears to mediate cell cycle arrest and regulate the timely activation of replication origins in the presence of unrepaired UV‐induced lesions. In fact, Mec1 and Rad53, but not Rad9 and the Rad24 group of checkpoint proteins, are required to delay cell cycle progression in rad14Δ cells after UV damage in G1… 
Requirement of Replication Checkpoint Protein Kinases Mec1/Rad53 for Postreplication Repair in Yeast
TLDR
Postreplication repair (PRR) of newly synthesized DNA in UV-damaged yeast cells is inhibited in the absence of Mec1 and Rad53 proteins, suggesting that lesion bypass in Saccharomyces cerevisiae cells occurs in conjunction with the stalled replication forks and not in gaps.
The yeast DNA damage checkpoint proteins control a cytoplasmic response to DNA damage
TLDR
The G2/M arrest in rad53Δ and chk1Δ revealed a unique cytoplasmic phenotype in which there are frequent dynein-dependent excursions of the nucleus through the bud neck, without entering anaphase, suggesting that Mec1-dependent checkpoint signaling through Rad53 and Chk1 includes the repression of nuclear movements that are normally associated with the execution of anaphases.
A Tel1/MRX-Dependent Checkpoint Inhibits the Metaphase-to-Anaphase Transition after UV Irradiation in the Absence of Mec1
TLDR
It is found that UV irradiation in G1 in the absence of Mec1 activates a Tel1/MRX-dependent checkpoint, which specifically inhibits the metaphase-to-anaphase transition in mec1Δ cells, suggesting that Pds1 persistence may be responsible for the inability to undergo anaphase.
Role of DNA damage-induced replication checkpoint in promoting lesion bypass by translesion synthesis in yeast.
TLDR
It is shown that proficient TLS can occur in the absence of these checkpoint proteins in nucleotide excision repair (NER)-proficient cells; however, in the presence of NER, checkpoint protein-mediated Rev1 phosphorylation contributes to increasing the proficiency of DNA polymerase zeta-dependent TLS.
Intra-G1 arrest in response to UV irradiation in fission yeast
TLDR
The response of Schizosaccharomyces pombe cells to UV irradiation in early G1 phase is studied and it is found that irradiation results in delayed progression through G1, as manifested most critically in the delayed formation of the pre-replication complex.
Postreplication gaps at UV lesions are signals for checkpoint activation
TLDR
Quantitative flow cytometry revealed that cells lacking translesion polymerases replicate UV-damaged DNA at the same rate at WT cells, indicating that the enhanced checkpoint response of cells lacking Polκ and Polη is not the result of stalled replication forks.
UV irradiation induces a postreplication DNA damage checkpoint
TLDR
An important physiological role of the cell-cycle response to UV is to provide time for postreplication repair in eukaryotic cells irradiated with high doses of UV.
Robust G1 checkpoint arrest in budding yeast: dependence on DNA damage signaling and repair.
TLDR
G1 delay is the predominant response to continuous gamma irradiation at a dose that confers no loss of viability but delays cell division and free DNA ends and/or single-stranded DNA are necessary and sufficient to induce a bona fide G1 checkpoint arrest.
Coordination of DNA damage tolerance mechanisms with cell cycle progression in fission yeast
TLDR
It is reported that checkpoint-dependent mitotic delay provides a cellular mechanism to ensure the completion of high fidelity DDT, largely by homology-directed repair (HDR).
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References

SHOWING 1-10 OF 88 REFERENCES
The budding yeast Rad9 checkpoint protein is subjected to Mec1/Tel1‐dependent hyperphosphorylation and interacts with Rad53 after DNA damage
TLDR
Damage‐induced hyperphosphorylation of Rad9 correlated with checkpoint functions (cell‐cycle arrest and transcriptional induction) and was cell‐cycle stage‐ and progression‐independent and analysis of checkpoint protein interactions after DNA damage revealed that Rad9 physically associates with Rad53.
Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair.
TLDR
It is concluded that the checkpoint in budding yeast consists of overlapping S-phase and G2-phase pathways that respond to incomplete DNA replication and/or DNA damage and cause arret of cells before mitosis.
RAD9 and DNA polymerase epsilon form parallel sensory branches for transducing the DNA damage checkpoint signal in Saccharomyces cerevisiae.
TLDR
Results show that POL2 and RAD9 function in parallel branches for sensing and transducing the UV DNA damage signal and indicate that RAD53 functions downstream of both these genes.
RAD9 and RAD24 define two additive, interacting branches of the DNA damage checkpoint pathway in budding yeast normally required for Rad53 modification and activation
TLDR
It is reported that efficient DDR induction requires all the above‐mentioned checkpoint genes and that RAD9 and the RAD24 epistasis group can be placed onto two separate, additive branches that converge on MEC1 and RAD53.
The anaphase inhibitor of Saccharomyces cerevisiae Pds1p is a target of the DNA damage checkpoint pathway.
  • O. Cohen-Fix, D. Koshland
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
TLDR
It is shown that DNA damage, but not inhibition of DNA replication, induces the phosphorylation of Pds1p, a downstream target of the DNA damage checkpoint pathway and that it is involved in implementing theDNA damage checkpoint arrest specifically in mitosis.
The Saccharomyces cerevisiae RAD9, RAD17, RAD24 and MEC3 genes are required for tolerating irreparable, ultraviolet-induced DNA damage.
TLDR
The effects of mutations that impair S phase regulation on the ability of excision repair-defective cells to replicate irreparably UV-damaged DNA are determined and RAD9, RAD17, RAD24, and MEC3 are found to be required for UV-induced mutagenesis and RAD 9 and RAD17 are required for maximal induction of replication-dependent sister chromatid exchange.
Rad53-dependent phosphorylation of Swi6 and down-regulation of CLN1 and CLN2 transcription occur in response to DNA damage in Saccharomyces cerevisiae.
TLDR
It is suggested that the Rad53-dependent phosphorylation of Swi6 may delay the transition to S phase by inhibiting CLN transcription.
RAD9, RAD17, and RAD24 are required for S phase regulation in Saccharomyces cerevisiae in response to DNA damage.
TLDR
It is shown that other genes involved in the DNA damage checkpoint pathway also play a role in regulating S phase in response to DNA damage, and the triple rad9 delta rad17 delta rad24 delta mutant also has a less severe defect than mec1-1 or rad53 mutants.
The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae.
TLDR
Examinations of the genetic basis for this response in the yeast Saccharomyces cerevisiae indicate that the RAD9 gene product is essential for arrest of cell division induced by DNA damage.
Regulation of DNA-replication origins during cell-cycle progression
TLDR
The effects of a DNA-damaging agent, methyl methane sulphonate (MMS), and of mutations in checkpoint genes such as rad53 on the activity of origins and on cell-cycle progression are studied, measured by two-dimensional gel analysis and by fluorescence-activated cell sorting.
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