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Diploid-specific [corrected] genome stability genes of S. cerevisiae: genomic screen reveals haploidization as an escape from persisting DNA rearrangement stress.

Alabrudzinska M, Skoneczny M, Skoneczna A - PLoS ONE (2011)

Bottom Line: We postulate that this phenomenon might diminish the devastating effects of DNA rearrangements, thereby increasing the cell's chances of surviving stressful conditions.We believe that numerous new genes implicated in genome maintenance, together with newly discovered phenomenon of ploidy reduction, will help revealing novel molecular processes involved in the genome stability of diploid cells.They also provide the clues in the quest for new therapeutic targets to cure human genome instability-related diseases.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Mutagenesis and DNA Repair, Institute of Biochemistry and Biophysics, Polish Academy of Science, Warsaw, Poland.

ABSTRACT
Maintaining a stable genome is one of the most important tasks of every living cell and the mechanisms ensuring it are similar in all of them. The events leading to changes in DNA sequence (mutations) in diploid cells occur one to two orders of magnitude more frequently than in haploid cells. The majority of those events lead to loss of heterozygosity at the mutagenesis marker, thus diploid-specific genome stability mechanisms can be anticipated. In a new global screen for spontaneous loss of function at heterozygous forward mutagenesis marker locus, employing three different mutagenesis markers, we selected genes whose deletion causes genetic instability in diploid Saccharomyces cerevisiae cells. We have found numerous genes connected with DNA replication and repair, remodeling of chromatin, cell cycle control, stress response, and in particular the structural maintenance of chromosome complexes. We have also identified 59 uncharacterized or dubious ORFs, which show the genome instability phenotype when deleted. For one of the strongest mutators revealed in our screen, ctf18Δ/ctf18Δ the genome instability manifests as a tendency to lose the whole set of chromosomes. We postulate that this phenomenon might diminish the devastating effects of DNA rearrangements, thereby increasing the cell's chances of surviving stressful conditions. We believe that numerous new genes implicated in genome maintenance, together with newly discovered phenomenon of ploidy reduction, will help revealing novel molecular processes involved in the genome stability of diploid cells. They also provide the clues in the quest for new therapeutic targets to cure human genome instability-related diseases.

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Related in: MedlinePlus

Comparison of genome-wide SLM screen results for CAN1 and URA3 markers.SLM screen results expressed as averaged LogRatio of relative abundance of each deletion clone obtained for CAN1 and URA3 markers were plotted against each other. LogRatio data derived only from the screens for mutator phenotypes show little correlation (A), whereas after subtracting the LogRatio data expressing resistance to the selection conditions and the LogRatio data expressing growth rate for each deletion strain (B) such a correlation exists.
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pone-0021124-g001: Comparison of genome-wide SLM screen results for CAN1 and URA3 markers.SLM screen results expressed as averaged LogRatio of relative abundance of each deletion clone obtained for CAN1 and URA3 markers were plotted against each other. LogRatio data derived only from the screens for mutator phenotypes show little correlation (A), whereas after subtracting the LogRatio data expressing resistance to the selection conditions and the LogRatio data expressing growth rate for each deletion strain (B) such a correlation exists.

Mentions: For every gene the value of LogRatio expressing overrepresentation of deletion clone due to its resistance to canavanine and LogRatio expressing underrepresentation of deletion clone due to its slow growth were subtracted from the LogRatio defining the level of SLM for that clone obtained with CAN1 marker. Likewise, LogRatios expressing resistance to 5′-FOA together with LogRatio expressing slow growth phenotype were subtracted from LogRatios defining the level of SLM with URA3 marker. Figure 1 shows the comparison, in the form of a correlation plot, of LogRatios derived from CAN1 SLM screen vs LogRatios derived from URA3 screen, with (B) and without (A) subtracting the resistance and slow growth LogRatios. As can be seen, the inclusion of these controls increases the correlation between SLM results for canavanine and that for 5′-FOA. This post-processing of large scale data increased also the correlation between those data and the results of semi-quantitative spontaneous mutagenesis tests done on selected individual deletion clones (see below).


Diploid-specific [corrected] genome stability genes of S. cerevisiae: genomic screen reveals haploidization as an escape from persisting DNA rearrangement stress.

Alabrudzinska M, Skoneczny M, Skoneczna A - PLoS ONE (2011)

Comparison of genome-wide SLM screen results for CAN1 and URA3 markers.SLM screen results expressed as averaged LogRatio of relative abundance of each deletion clone obtained for CAN1 and URA3 markers were plotted against each other. LogRatio data derived only from the screens for mutator phenotypes show little correlation (A), whereas after subtracting the LogRatio data expressing resistance to the selection conditions and the LogRatio data expressing growth rate for each deletion strain (B) such a correlation exists.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3117874&req=5

pone-0021124-g001: Comparison of genome-wide SLM screen results for CAN1 and URA3 markers.SLM screen results expressed as averaged LogRatio of relative abundance of each deletion clone obtained for CAN1 and URA3 markers were plotted against each other. LogRatio data derived only from the screens for mutator phenotypes show little correlation (A), whereas after subtracting the LogRatio data expressing resistance to the selection conditions and the LogRatio data expressing growth rate for each deletion strain (B) such a correlation exists.
Mentions: For every gene the value of LogRatio expressing overrepresentation of deletion clone due to its resistance to canavanine and LogRatio expressing underrepresentation of deletion clone due to its slow growth were subtracted from the LogRatio defining the level of SLM for that clone obtained with CAN1 marker. Likewise, LogRatios expressing resistance to 5′-FOA together with LogRatio expressing slow growth phenotype were subtracted from LogRatios defining the level of SLM with URA3 marker. Figure 1 shows the comparison, in the form of a correlation plot, of LogRatios derived from CAN1 SLM screen vs LogRatios derived from URA3 screen, with (B) and without (A) subtracting the resistance and slow growth LogRatios. As can be seen, the inclusion of these controls increases the correlation between SLM results for canavanine and that for 5′-FOA. This post-processing of large scale data increased also the correlation between those data and the results of semi-quantitative spontaneous mutagenesis tests done on selected individual deletion clones (see below).

Bottom Line: We postulate that this phenomenon might diminish the devastating effects of DNA rearrangements, thereby increasing the cell's chances of surviving stressful conditions.We believe that numerous new genes implicated in genome maintenance, together with newly discovered phenomenon of ploidy reduction, will help revealing novel molecular processes involved in the genome stability of diploid cells.They also provide the clues in the quest for new therapeutic targets to cure human genome instability-related diseases.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Mutagenesis and DNA Repair, Institute of Biochemistry and Biophysics, Polish Academy of Science, Warsaw, Poland.

ABSTRACT
Maintaining a stable genome is one of the most important tasks of every living cell and the mechanisms ensuring it are similar in all of them. The events leading to changes in DNA sequence (mutations) in diploid cells occur one to two orders of magnitude more frequently than in haploid cells. The majority of those events lead to loss of heterozygosity at the mutagenesis marker, thus diploid-specific genome stability mechanisms can be anticipated. In a new global screen for spontaneous loss of function at heterozygous forward mutagenesis marker locus, employing three different mutagenesis markers, we selected genes whose deletion causes genetic instability in diploid Saccharomyces cerevisiae cells. We have found numerous genes connected with DNA replication and repair, remodeling of chromatin, cell cycle control, stress response, and in particular the structural maintenance of chromosome complexes. We have also identified 59 uncharacterized or dubious ORFs, which show the genome instability phenotype when deleted. For one of the strongest mutators revealed in our screen, ctf18Δ/ctf18Δ the genome instability manifests as a tendency to lose the whole set of chromosomes. We postulate that this phenomenon might diminish the devastating effects of DNA rearrangements, thereby increasing the cell's chances of surviving stressful conditions. We believe that numerous new genes implicated in genome maintenance, together with newly discovered phenomenon of ploidy reduction, will help revealing novel molecular processes involved in the genome stability of diploid cells. They also provide the clues in the quest for new therapeutic targets to cure human genome instability-related diseases.

Show MeSH
Related in: MedlinePlus