Novel checkpoint pathway organization promotes genome stability in stationary-phase yeast cells

Bonnie Alver, Maire K. Kelly, David T Kirkpatrick

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Most DNA alterations occur during DNA replication in the S phase of the cell cycle. However, the majority of eukaryotic cells exist in a nondividing, quiescent state. Little is known about the factors involved in preventing DNA instability within this stationary- phase cell population. Previously, we utilized a unique assay system to identify mutations that increased minisatellite alterations specifically in quiescent cells in Saccharomyces cerevisiae. Here we conducted a modified version of synthetic genetic array analysis to determine if checkpoint signaling components play a role in stabilizing minisatellites in stationary-phase yeast cells. Our results revealed that a subset of checkpoint components, specifically MRC1, CSM3, TOF1, DDC1, RAD17, MEC3, TEL1, MEC1, and RAD53, prevent stationary-phase minisatellite alterations within the quiescent cell subpopulation of stationary- phase cells. Pathway analysis revealed at least three pathways, with MRC1, CSM3, and TOF1 acting in a pathway independent of MEC1 and RAD53. Overall, our data indicate that some well-characterized checkpoint components maintain minisatellite stability in stationary-phase cells but are regulated differently in those cells than in actively growing cells. For the MRC1- dependent pathway, the checkpoint itself may not be the important element; rather, it may be loss of the checkpoint proteins' other functions that contributes to DNA instability.

Original languageEnglish (US)
Pages (from-to)457-472
Number of pages16
JournalMolecular and Cellular Biology
Volume33
Issue number2
DOIs
StatePublished - Jan 1 2013

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Genomic Instability
Yeasts
Minisatellite Repeats
DNA
Eukaryotic Cells
DNA Replication
S Phase
Saccharomyces cerevisiae
Cell Cycle
Mutation
Population

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Novel checkpoint pathway organization promotes genome stability in stationary-phase yeast cells. / Alver, Bonnie; Kelly, Maire K.; Kirkpatrick, David T.

In: Molecular and Cellular Biology, Vol. 33, No. 2, 01.01.2013, p. 457-472.

Research output: Contribution to journalArticle

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