title: The Transient Inactivation of the Master Cell Cycle Phosphatase Cdc14 Causes Genomic Instability in Diploid Cells of Saccharomyces cerevisiae.
abstract: Genomic instability is a common feature found in cancer cells . Accordingly, many tumor suppressor genes identified in familiar cancer syndromes are involved in the maintenance of the stability of the genome during every cell division and are commonly referred to as caretakers. Inactivating mutations and epigenetic silencing of caretakers are thought to be the most important mechanisms that explain cancer-related genome instability. However, little is known of whether transient inactivation of caretaker proteins could trigger genome instability and, if so, what types of instability would occur. In this work, we show that a brief and reversible inactivation, during just one cell cycle, of the key phosphatase Cdc14 in the model organism Saccharomyces cerevisiae is enough to result in diploid cells with multiple gross chromosomal rearrangements and changes in ploidy. Interestingly, we observed that such transient loss yields a characteristic fingerprint whereby trisomies are often found in small-sized chromosomes, and gross chromosome rearrangements, often associated with concomitant loss of heterozygosity, are detected mainly on the ribosomal DNA-bearing chromosome XII. Taking into account the key role of Cdc14 in preventing anaphase bridges, resetting replication origins, and controlling spindle dynamics in a well-defined window within anaphase, we speculate that the transient loss of Cdc14 activity causes cells to go through a single mitotic catastrophe with irreversible consequences for the genome stability of the progeny.
authors.affiliation: Unidad de Investigación, Hospital Universitario Nuestra Señora de la Candelaria, 38010 Santa Cruz de Tenerife, Spain.
authors.forename: Oliver
authors.initials: O
authors.lastname: Quevedo
authors.affiliation: Unidad de Investigación, Hospital Universitario Nuestra Señora de la Candelaria, 38010 Santa Cruz de Tenerife, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ramos-Pérez
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710 tom.petes@duke.edu fmacconw@gmail.com.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Petes
authors.affiliation: Unidad de Investigación, Hospital Universitario Nuestra Señora de la Candelaria, 38010 Santa Cruz de Tenerife, Spain tom.petes@duke.edu fmacconw@gmail.com.
authors.forename: Félix
authors.identifier: http://orcid.org/0000-0003-4559-7798
authors.initials: F
authors.lastname: Machín
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D002869:Chromosome Aberrations; D015825:Chromosomes, Fungal; D004171:Diploidy; D017353:Gene Deletion; D042822:Genomic Instability; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
chemical_list: C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D017027:Protein Tyrosine Phosphatases
keywords: Cdc14; Saccharomyces cerevisiae; aneuploidy; caretaker genes; gross chromosomal rearrangements