Dataset Information

Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae.

ABSTRACT: In mammalian cells, perturbations in DNA replication result in chromosome breaks in regions termed "fragile sites." Using DNA microarrays, we mapped recombination events and chromosome rearrangements induced by reduced levels of the replicative DNA polymerase-? in the yeast Saccharomyces cerevisiae. We found that the recombination events were nonrandomly associated with a number of structural/sequence motifs that correlate with paused DNA replication forks, including replication-termination sites (TER sites) and binding sites for the helicase Rrm3p. The pattern of gene-conversion events associated with cross-overs suggests that most of the DNA lesions that initiate recombination between homologs are double-stranded DNA breaks induced during S or G2 of the cell cycle, in contrast to spontaneous recombination events that are initiated by double-stranded DNA breaks formed prior to replication. Low levels of DNA polymerase-? also induced very high rates of aneuploidy, as well as chromosome deletions and duplications. Most of the deletions and duplications had Ty retrotransposons at their breakpoints.

SUBMITTER: Song W

PROVIDER: S-EPMC4040566 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae.

Song Wei W Dominska Margaret M Greenwell Patricia W PW Petes Thomas D TD

Proceedings of the National Academy of Sciences of the United States of America 20140505 21

In mammalian cells, perturbations in DNA replication result in chromosome breaks in regions termed "fragile sites." Using DNA microarrays, we mapped recombination events and chromosome rearrangements induced by reduced levels of the replicative DNA polymerase-α in the yeast Saccharomyces cerevisiae. We found that the recombination events were nonrandomly associated with a number of structural/sequence motifs that correlate with paused DNA replication forks, including replication-termination site ...[more]

PMID: 24799712

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Project description:UNLABELLED:In the model eukaryote Saccharomyces cerevisiae, the transcription factor Cst6p has been reported to play important roles in several biological processes. However, the genome-wide targets of Cst6p and its physiological functions remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high resolution. Cst6p binds to the promoter regions of 59 genes with various biological functions when cells are grown on ethanol but hardly binds to the promoter at any gene when cells are grown on glucose. The retarded growth of the CST6 deletion mutant on ethanol is attributed to the markedly decreased expression of NCE103, encoding a carbonic anhydrase, which is a direct target of Cst6p. The target genes of Cst6p have a large overlap with those of stress-responsive transcription factors, such as Sko1p and Skn7p. In addition, a CST6 deletion mutant growing on ethanol shows hypersensitivity to oxidative stress and ethanol stress, assigning Cst6p as a new member of the stress-responsive transcriptional regulatory network. These results show that mapping of genome-wide binding sites can provide new insights into the function of transcription factors and highlight the highly connected and condition-dependent nature of the transcriptional regulatory network in S. cerevisiae IMPORTANCE:Transcription factors regulate the activity of various biological processes through binding to specific DNA sequences. Therefore, the determination of binding positions is important for the understanding of the regulatory effects of transcription factors. In the model eukaryote Saccharomyces cerevisiae, the transcription factor Cst6p has been reported to regulate several biological processes, while its genome-wide targets remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high resolution. We show that the binding of Cst6p to its target promoters is condition dependent and explain the mechanism for the retarded growth of the CST6 deletion mutant on ethanol. Furthermore, we demonstrate that Cst6p is a new member of a stress-responsive transcriptional regulatory network. These results provide deeper understanding of the function of the dynamic transcriptional regulatory network in S. cerevisiae.

Dataset Information

Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae.

Publications

Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae.

Similar Datasets

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