Genomics

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Elevated Levels of Aneuploidy and Chromosome Rearrangements are Separable Genome Instability Events


ABSTRACT: In Saccharomyces cerevisiae, Elevated Levels of Aneuploidy and Chromosome Rearrangements are Separable Genome Instability Events Controlled by the Tel1 and Mec1 Kinases Cancer cells often have elevated frequencies of chromosomal aberrations, and it is likely that loss of genome stability is one driving force behind tumorigenesis. Deficiencies in DNA replication, DNA repair, or cell cycle checkpoints can all contribute to increased rates of chromosomal duplications, deletions and translocations. The Saccharomyces cerevisiae proteins Tel1 and Mec1 (homologues of the human ATM and ATR proteins, respectively) are known to participate in the DNA damage response, replication checkpoint, and telomere maintenance pathways and are critical to maintain genome stability. In the absence of induced DNA damage, tel1 mec1 diploid yeast strains exhibit extremely high rates of chromosome aneuploidy. There is a significant bias towards trisomy of chromosomes II, VIII, X, and XII, whereas the smallest chromosomes I and VI are commonly monosomic. tel1 mec1 strains also demonstrate elevated levels of chromosome rearrangements, including translocations as well as interstitial duplications and deletions. Restoring wild-type telomere length with the Cdc13-Est2 fusion protein substantially reduces the amount of chromosome rearrangements in tel1 mec1 strains. This result suggests that most of the rearrangements are initiated by telomere-telomere fusions. However, the telomere defects associated with tel1 mec1 strains do not cause the high rate of aneuploidy, as restoring proper telomere function does not prevent cells from becoming aneuploid. Our data demonstrate that the same mutant genotype can produce both high levels of chromosome rearrangements and high levels of aneuploidy, and these two types of events occur through separate mechanisms.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE17903 | GEO | 2009/09/03

SECONDARY ACCESSION(S): PRJNA119971

REPOSITORIES: GEO

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