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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

PFGE analysis of chromosomes from 2n ctf18 clones before and after prolonged growth.PFGE analysis of chromosomes isolated from eight freshly prepared 2n ctf18 clones (numbered 1 to 8) and from the same clones grown for 240 generations. See Materials and Methods for detailes.
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pone-0021124-g006: PFGE analysis of chromosomes from 2n ctf18 clones before and after prolonged growth.PFGE analysis of chromosomes isolated from eight freshly prepared 2n ctf18 clones (numbered 1 to 8) and from the same clones grown for 240 generations. See Materials and Methods for detailes.

Mentions: To exclude the possibility that DNA content differences between the 2n ctf18 strains after 240 generations arose from severe chromosomal aberrations rather than ploidy reduction we analyzed the sizes of chromosomes of eight ctf18Δ/ctf18Δ clones before and after 240 generations by Pulsed-Field Gel Electrophoresis (PFGE). As shown on Figure 6 there are no visible differences in mobility and sharpness of chromosome bands between freshly made clones and those that underwent 240 generations irrespective of the DNA content.


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)

PFGE analysis of chromosomes from 2n ctf18 clones before and after prolonged growth.PFGE analysis of chromosomes isolated from eight freshly prepared 2n ctf18 clones (numbered 1 to 8) and from the same clones grown for 240 generations. See Materials and Methods for detailes.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0021124-g006: PFGE analysis of chromosomes from 2n ctf18 clones before and after prolonged growth.PFGE analysis of chromosomes isolated from eight freshly prepared 2n ctf18 clones (numbered 1 to 8) and from the same clones grown for 240 generations. See Materials and Methods for detailes.
Mentions: To exclude the possibility that DNA content differences between the 2n ctf18 strains after 240 generations arose from severe chromosomal aberrations rather than ploidy reduction we analyzed the sizes of chromosomes of eight ctf18Δ/ctf18Δ clones before and after 240 generations by Pulsed-Field Gel Electrophoresis (PFGE). As shown on Figure 6 there are no visible differences in mobility and sharpness of chromosome bands between freshly made clones and those that underwent 240 generations irrespective of the DNA content.

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