Gene overexpression screen for chromosome instability in yeast primarily identifies cell cycle progression genes.

Abstract:

:Loss of heterozygosity (LOH) in a vegetatively growing diploid cell signals irregularity of mitosis. Therefore, assays of LOH serve to discover pathways critical for proper replication and segregation of chromosomes. We screened for enhanced LOH in a whole-genome collection of diploid yeast strains in which a single gene was strongly overexpressed. We found 39 overexpression strains with substantially increased LOH caused either by recombination or by chromosome instability. Most of them, 32 in total, belonged to the category of "cell division", a broadly defined biological process. Of those, only one, TOP3, coded for an enzyme that uses DNA as a substrate. The rest related to establishment and maintenance of cell polarity, chromosome segregation, and cell cycle checkpoints. Former studies, in which gene deletions were used, showed that an absence of a protein participating in the DNA processing machinery is a potent stimulator of genome instability. As our results suggest, overexpression of such proteins is not comparably damaging as the absence of them. It may mean that the harmful effect of overexpression is more likely to occur in more complex and multistage processes, such as chromosome segregation. We also report a side finding, resulting from the fact that we worked with the yeast strains bearing a 2-micron plasmid. We noted that intense transcription from such a plasmid led to an enhanced rate of an entire chromosome loss (as opposed to LOH produced by recombination). This observation may support models linking segregation of 2-micron plasmids to segregation of chromosomes.

journal_name

Curr Genet

journal_title

Current genetics

authors

Tutaj H,Pogoda E,Tomala K,Korona R

doi

10.1007/s00294-018-0885-x

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

483-492

issue

2

eissn

0172-8083

issn

1432-0983

pii

10.1007/s00294-018-0885-x

journal_volume

65

pub_type

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