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Genetic alterations leading to increases in internal potassium concentrations are detrimental for DNA integrity in Saccharomyces cerevisiae
Author(s) -
Merchan Stephanie,
Pedelini Leda,
Hueso Guillem,
Calzada Arturo,
Serrano Ramón,
Yenush Lynne
Publication year - 2011
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2010.01472.x
Subject(s) - biology , saccharomyces cerevisiae , mutant , dna damage , dna repair , cell cycle , microbiology and biotechnology , homologous recombination , dna replication , gene , dna , phenotype , mutation , biochemistry
We have investigated the effects of alterations in potassium homeostasis on cell cycle progression and genome stability in Saccharomyces cerevisiae . Yeast strains lacking the PPZ1 and PPZ2 phosphatase genes, which aberrantly accumulate potassium, are sensitive to agents causing replicative stress or DNA damage and present a cell cycle delay in the G 1 /S phase. A synthetic slow growth phenotype was identified in a subset of DNA repair mutants upon inhibition of Ppz activity. Moreover, we observe that this slow growth phenotype observed in cdc7 ts mutants with reduced Ppz activity is reverted by disrupting the TRK1 potassium transporter gene. As over‐expression of a mammalian potassium transporter leads to similar phenotypes, we conclude that these defects can be attributed to potassium accumulation. As we reported previously, internal potassium accumulation activates the Slt2 MAP kinase pathway. We show that the removal of SLT2 in ppz1 ppz2 mutants ameliorates sensitivity to agents causing replication stress and DNA damage, whereas over‐activation of the pathway leads to similar cell cycle‐related defects. Taken together, these results are consistent with inappropriate potassium accumulation reducing DNA replication efficiency, negatively influencing DNA integrity and leading to the requirement of mismatch repair, the MRX complex, or homologous recombination pathways for normal growth.