Genetic changes and bioassays in bleomycin- and phleomycin-treated cells, and their relationship to chromosomal breaks

Mc.Koy, Judith F.; Pleninger, Perrin; Wall, Laurel; Pramanik, Ajay; M, Martinez; Moore, Carol W.

doi:10.1016/0921-8777(94)00040-d

Cited by 19 publications

(2 citation statements)

References 17 publications

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“…Using a genome‐wide screen in S. cerevisiae , we identified the mutant lsm1 Δ as hypersensitive to trabectedin, a DNA‐binding drug that causes replication‐dependent double‐strand breaks (DSBs) (Herrero et al , 2006; Guirouilh‐Barbat et al , 2008). We then examined the sensitivity of lsm1 Δ to other DNA‐damaging agents, methyl methanesulfonate (MMS), campthotecin (CPT), phleomycin (Phl) and hydroxyurea (HU), which have been reported to induce DSBs directly or indirectly (Koy et al , 1995; Petermann et al , 2010). lsm1 Δ cells were highly sensitive to MMS, CPT and HU and moderately sensitive to Phl (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

Lsm1 promotes genomic stability by controlling histone mRNA decay

Herrero

Moreno

2011

The EMBO Journal

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Lsm1 forms part of a cytoplasmic protein complex, Lsm1-7-Pat1, involved in the degradation of mRNAs. Here, we show that Lsm1 has an important role in promoting genomic stability in Saccharomyces cerevisiae. Budding yeast cells lacking Lsm1 are defective in recovery from replication-fork stalling and show DNA damage sensitivity. Here, we identify histone mRNAs as substrates of the Lsm1-7-Pat1 complex in yeast, and show that abnormally high amounts of histones accumulate in lsm1D mutant cells. Importantly, we show that the excess of histones is responsible for the lsm1D replication-fork instability phenotype, since sensitivity of lsm1D cells to drugs that stall replication forks is significantly suppressed by a reduction in histone gene dosage. Our results demonstrate that improper histone stoichiometry leads to genomic instability and highlight the importance of regulating histone mRNA decay in the tight control of histone levels in yeast.

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Section: Resultsmentioning

confidence: 99%

Lsm1 promotes genomic stability by controlling histone mRNA decay

Herrero

Moreno

2011

The EMBO Journal

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“…We utilized this system, without introducing exogenous p53, to test for transactivation capabilities of a yeast protein or protein complex in response to DNA damage. We used phleomycin D1 to introduce DNA damage, including double-strand breaks, into cellular DNAs [40,[66][67][68]. As described in the Figure 6 legend, one wild-type ADE2 strain without the P21-5′ and Con-A RE's, and two mutant ade2 strains without the P21-5′ and Con-A RE's, were used as controls in all experiments.…”

Section: Dna-damage Inducible Regulation Of Transactivation From Repomentioning

confidence: 99%

A Protein in the Yeast Saccharomyces cerevisiae Presents DNA Binding Homology to the p53 Checkpoint Protein and Tumor Suppressor

et al. 2020

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Saccharomyces cerevisiae does not contain a p53 homolog. Utilizing this yeast as an in vivo test tube model, our aim was to investigate if a yeast protein would show p53 DNA binding homology. Electrophoretic mobility shift analyses revealed the formation of specific DNA-protein complexes consisting of S. cerevisiae nuclear protein(s) and oligonucleotides containing p53 DNA binding sites. A S. cerevisiae p53 binding site factor (Scp53BSF) bound to a p53 synthetic DNA-consensus sequence (SCS) and a p53 binding-site sequence from the MDM2 oncogene. The complexes were of comparable size. Like mammalian p53, the affinity of Scp53BSF for the SCS oligonucleotide was higher than for the MDM2 oligonucleotide. Binding of Scp53BSF to the SCS and MDM2 oligonucleotides was strongly competed by unlabeled oligonucleotides containing mammalian p53 sites, but very little by a mutated site oligonucleotide. Importantly, Scp53BSF-DNA binding activity was significantly induced in extracts from cells with DNA damage. This resulted in dose-dependent coordinated activation of transcription when using p53-binding site reporter constructs. An ancient p53-like DNA binding protein may have been found, and activation of DNA-associated factors to p53 response elements may have functions not yet determined.

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Bleomycin

Moore¹

2002

Encyclopedia of Molecular Biology

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Genetic changes and bioassays in bleomycin- and phleomycin-treated cells, and their relationship to chromosomal breaks

Cited by 19 publications

References 17 publications

Lsm1 promotes genomic stability by controlling histone mRNA decay

Lsm1 promotes genomic stability by controlling histone mRNA decay

A Protein in the Yeast Saccharomyces cerevisiae Presents DNA Binding Homology to the p53 Checkpoint Protein and Tumor Suppressor

Bleomycin

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