title: Novel checkpoint pathway organization promotes genome stability in stationary-phase yeast cells.
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.
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Alver
authors.forename: Maire K
authors.initials: MK
authors.lastname: Kelly
authors.forename: David T
authors.initials: DT
authors.lastname: Kirkpatrick
mesh_terms: D002453:Cell Cycle; D059447:Cell Cycle Checkpoints; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D042822:Genomic Instability; D018598:Minisatellite Repeats; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins