title: Cdc14 phosphatase: warning, no delay allowed for chromosome segregation!
abstract: Cycling events in nature start and end to restart again and again. In the cell cycle, whose purpose is to become two where there was only one, cyclin-dependent kinases (CDKs) are the beginning and, therefore, phosphatases must play a role in the ending. Since CDKs are drivers of the cell cycle and cancer cells uncontrollably divide, much attention has been put into knocking down CDK activity. However, much less is known on the consequences of interfering with the phosphatases that put an end to the cell cycle. We have addressed in recent years the consequences of transiently inactivating the only master cell cycle phosphatase in the model yeast Saccharomyces cerevisiae, Cdc14. Transient inactivation is expected to better mimic the pharmacological action of drugs. Interestingly, we have found that yeast cells tolerate badly a relatively brief inactivation of Cdc14 when cells are already committed into anaphase, the first cell cycle stage where this phosphatase plays important roles. First, we noticed that the segregation of distal regions in the chromosome arm that carries the ribosomal DNA array was irreversibly impaired, leading to an anaphase bridge (AB). Next, we found that this AB could eventually be severed by cytokinesis and led to two different types of genetically compromised daughter cells. All these previous studies were done in haploid cells. We have now recently expanded this analysis to diploid cells and used the advantage of making hybrid diploids to study chromosome rearrangements and changes in the ploidy of the surviving progeny. We have found that the consequences for the genome integrity were far more dramatic than originally envisioned.
authors.affiliation: Unidad de Investigación, Hospital Universitario Nuestra Señora de la Candelaria, Ctra del Rosario 145, 38010, Santa Cruz de Tenerife, Spain. fmacconw@gmail.com.
authors.forename: Félix
authors.identifier: http://orcid.org/0000-0003-4559-7798
authors.initials: F
authors.lastname: Machín
authors.affiliation: Unidad de Investigación, Hospital Universitario Nuestra Señora de la Candelaria, Ctra del Rosario 145, 38010, Santa Cruz de Tenerife, Spain.|Center for Chromosome Stability and Department of Biology, University of Copenhagen, 2200, Copenhagen, Denmark.
authors.forename: Oliver
authors.initials: O
authors.lastname: Quevedo
authors.affiliation: Unidad de Investigación, Hospital Universitario Nuestra Señora de la Candelaria, Ctra del Rosario 145, 38010, Santa Cruz de Tenerife, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ramos-Pérez
authors.affiliation: Unidad de Investigación, Hospital Universitario Nuestra Señora de la Candelaria, Ctra del Rosario 145, 38010, Santa Cruz de Tenerife, Spain.|Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London, W12 0NN, UK.
authors.forename: Jonay
authors.initials: J
authors.lastname: García-Luis
mesh_terms: D000705:Anaphase / Q000235:genetics; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal; D008938:Mitosis; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D012854:Sister Chromatid Exchange
chemical_list: C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D017027:Protein Tyrosine Phosphatases
keywords: Anaphase bridges; Aneuploidy; Cdc14; Gross chromosomal rearrangements; Saccharomyces cerevisiae; rDNA